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Zhang Y, Scholten D, Qiang W, Platanias LC, Gradishar WJ, Kelley SO, Liu H. Circulation tumor cell isolation and enrichment technologies. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2025; 392:119-149. [PMID: 40287218 DOI: 10.1016/bs.ircmb.2025.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
During cancer metastasis, tumor cells migrate from the primary tumor site and spread to distant tissue or organs through the circulatory system of the body. While it is challenging to track metastatic tumor cells, circulating tumor cells (CTCs) via liquid biopsy provide a unique and important opportunity for longitudinal monitoring of residual cancer diseases and progression, showing great potential to facilitate precision medicine in cancer patients. The enumeration and characterization of CTCs represent prognostic and predictive biomarkers, which can be used to monitor the response to and efficacy of various therapies. Along with molecular and cellular features of CTCs, this data can inform the detection of early micro-metastases and assess progression of advanced disease in a more sensitive manner than traditional imaging modalities, serving as a complementary approach with added value. Nevertheless, comprehensive multiomic analyses of CTCs at inter-cellular (cluster), single-cell, and subcellular levels to elucidate relevant CTC cancer biology, tumor immune ecosystem biology, and clinical outcomes have yet to be achieved, demanding multidisciplinary collaboration to advance the field. Complementary to the published chapter on multiomic analyses and functional properties of CTCs, this chapter summarizes key methods and integrated strategies in CTC isolation, highlighting an accelerated evolution in high-throughput analysis of CTCs.
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Affiliation(s)
- Youbin Zhang
- Circulating Tumor Cell Core, Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, United States; Hematology & Oncology Division, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - David Scholten
- Driskill Graduate Program (DGP) in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Wenan Qiang
- Chemistry of Life Processes, Chicago, IL, United States
| | - Leonidas C Platanias
- Circulating Tumor Cell Core, Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, United States; Hematology & Oncology Division, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - William J Gradishar
- Circulating Tumor Cell Core, Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, United States; Hematology & Oncology Division, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Shana O Kelley
- Chemistry of Life Processes, Chicago, IL, United States; Department of Chemistry, Northwestern University, Chicago, IL, United States; Department of Biomedical Engineering, Northwestern University, Chicago, IL, United States; Chan Zuckerberg Biohub Chicago, Chicago, IL, United States
| | - Huiping Liu
- Circulating Tumor Cell Core, Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, United States; Hematology & Oncology Division, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Chan Zuckerberg Biohub Chicago, Chicago, IL, United States.
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Guo Z, Jin S, Yang M, Fu L, Ran Y, Yu Y, Wang W. Luminol/PtCo@rGO and Au@CNTs-based electrochemiluminescence cytosensor for ultrasensitive detection of breast cancer CTCs. Anal Chim Acta 2025; 1335:343452. [PMID: 39643306 DOI: 10.1016/j.aca.2024.343452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Breast cancer CTCs have recently been recognized as an emerging biomarker for liquid biopsy of breast cancer. In this work, based on two-dimensional (2D) noble metal PtCo@rGO nanozymes and Au@CNTs bioconjugates, a novel electrochemiluminescence (ECL) cytosensor was developed in order to detect breast cancer CTCs (MCF-7) ultrasensitively. RESULTS The PtCo@rGO nanozymes possessed large specific surface area and high efficiency peroxidase-like activity, which can be used as nanocarriers to anchor and catalyze luminol ECL emission efficiently. Moreover, the PtCo@rGO nanozymes have fractal nanostructures similar to that of CTCs and can capable of enhancing the adhesion of MCF-7 when assembled together with aptamers containing HS-modified epithelial specific cell adhesion molecules (EpCAM, S1). Importantly, the S1/Au@CNTs bioconjugates loaded on the glassy carbon electrode (GCE) can effectively capture MCF-7 cells. Benefiting from the above-mentioned advantages, the ECL cytosensor constructed for MCF-7 cells detection performed well with a wide linear range (2-1 × 104 cells mL-1) and a low limit of detection (1 cells mL-1). SIGNIFICANCE The designed ECL cytosensor could provide a promising platform for CTC-based liquid biopsy and have broad application prospects in breast cancer early diagnosis and prognostic monitoring.
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Affiliation(s)
- Zhen Guo
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Shenghang Jin
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Meiying Yang
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Luxuan Fu
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Yan Ran
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Yan Yu
- Center for Rehabilitation Medicine, Department of Ophthalmology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Weizhong Wang
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Leung LL, Qu X, Chen B, Chan JYK. Extracellular vesicles in liquid biopsies: there is hope for oral squamous cell carcinoma. EXTRACELLULAR VESICLES AND CIRCULATING NUCLEIC ACIDS 2024; 5:639-659. [PMID: 39811735 PMCID: PMC11725428 DOI: 10.20517/evcna.2024.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 06/29/2024] [Accepted: 11/20/2024] [Indexed: 01/16/2025]
Abstract
Current approaches to oral cancer diagnosis primarily involve physical examination, tissue biopsy, and advanced computer-aided imaging techniques. However, despite these advances, patient survival rates have not significantly improved. Hence, there is a critical need to develop minimally invasive tools with high sensitivity and specificity to improve patient survival and quality of life. Liquid biopsy is a non-invasive, real-time method for predicting cancer status and potentially serves as a biomarker source for treatment response. Liquid biopsy includes rich biologically relevant components, such as circulating tumor cells, circulating tumor DNA, and extracellular vesicles (EVs). EVs are particularly intriguing due to their relatively high abundance in most biofluids, with the potential to identify specific cargo derived from circulating tumor EVs. Moreover, normal cells in lymph nodes can uptake EVs, fostering a pre-metastatic microenvironment that facilitates lymph node metastases - a common occurrence in oral cancers. This review encompasses English language publications over the last twenty years, focusing on methods for isolating EVs from saliva, blood, and lymphatic fluids, as well as the collection methods employed. Seventeen cases met the inclusion criteria according to ISEV guidelines, including 10 saliva cases, 6 blood cases, and 1 lymphatic fluid case. This review also highlighted research gaps in oral squamous cell carcinoma (OSCC) EVs, including a lack of multi-omics studies and the exploration of potential EV markers for drug resistance, as well as a notable underutilization of microfluidic technologies to translate liquid biopsy EV findings into clinical applications.
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Affiliation(s)
| | | | | | - Jason YK. Chan
- Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong 00000, China
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Mishra S, Kumari S, Husain N. Liquid biopsy in gallbladder carcinoma: Current evidence and future prospective. THE JOURNAL OF LIQUID BIOPSY 2024; 6:100280. [PMID: 40027313 PMCID: PMC11863890 DOI: 10.1016/j.jlb.2024.100280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 03/05/2025]
Abstract
Although there have been significant advances in the early detection and treatment of gallbladder cancer (GBC), it is still considered a leading cause of morbidity and mortality. Molecular profiling of tumors is generally performed using samples obtained during surgery or biopsy. However, tissue genotyping has its limitations as it only provides a single snapshot and is susceptible to spatial selection bias due to the tumor heterogeneity. Over the past decade, there has been a remarkable transition from invasive diagnostic methods to non-invasive alternatives, including liquid biopsy, for cancer diagnosis and monitoring. Liquid biopsies have ushered in a new era in clinical oncology, enabling convenient tumor sampling, continuous monitoring through repeated analysis, development of personalized treatment regimens, and assessment of therapy resistance. While peripheral blood is the primary medium for these biopsies, other biological fluids, including urine, saliva, and bile, also serve as valuable sources of information. Currently, the focus of blood-based biopsy analyses is on four main sources of biomarkers for cancer detection and stratification: circulating tumor DNA (ctDNA) or circulating free DNA (cfDNA), circulating tumor cells (CTCs), and extracellular vesicle (EVs). There are over 300 clinical trials either ongoing or actively recruiting participants to investigate the diagnostic and prognostic applications of ctDNA/cfDNA in the context of cancer. This review outlines the current standard of care for individuals with GBC, anticipates future treatment developments, and evaluates the potential applications of liquid biopsies in various clinical contexts. The review addresses ctDNA/cfDNA, CTC, and circulating microRNA and highlights their prospective roles in management of GBC.
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Affiliation(s)
- Sridhar Mishra
- Department of Pathology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India
- Department of Plastic and Reconstructive Surgery, King George Medical University, Lucknow, Uttar 1pradesh, 226003, India
| | - Swati Kumari
- Department of Pathology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India
- Department of Pathology, King George Medical University, Lucknow, Uttar 1pradesh, 226003, India
| | - Nuzhat Husain
- Department of Pathology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India
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Dompé C, Chojnowska A, Ramlau R, Nowicki M, Alix-Panabières C, Budna-Tukan J. Unveiling the dynamics of circulating tumor cells in colorectal cancer: from biology to clinical applications. Front Cell Dev Biol 2024; 12:1498032. [PMID: 39539964 PMCID: PMC11557528 DOI: 10.3389/fcell.2024.1498032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
This review delves into the pivotal role of circulating tumor cells (CTCs) in colorectal cancer (CRC) metastasis, focusing on their biological properties, interactions with the immune system, advanced detection techniques, and clinical implications. We explored how metastasis-competent CTCs evade immune surveillance and proliferate, utilizing cutting-edge detection and isolation technologies, such as microfluidic devices and immunological assays, to enhance sensitivity and specificity. The review highlights the significant impact of CTC interactions with immune cells on tumor progression and patient outcomes. It discusses the application of these findings in clinical settings, including non-invasive liquid biopsies for early diagnosis, prognosis, and treatment monitoring. Despite advancements, challenges remain, such as the need for standardized methods to consistently capture and analyze CTCs. Addressing these challenges through further molecular and cellular research on CTCs could lead to improved interventions and outcomes for CRC patients, underscoring the importance of unraveling the complex dynamics of CTCs in cancer progression.
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Affiliation(s)
- Claudia Dompé
- Department of Immunology, Poznan University of Medical Sciences, Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Rodryg Ramlau
- Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland
| | - Michal Nowicki
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland
| | - Catherine Alix-Panabières
- Laboratory of Rare Human Circulating Cells and Liquid Biopsy (LCCRH), University Medical Centre of Montpellier, Montpellier, France
- Centre de Recherche en Ecologie et Evolution du Cancer, Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle, University of Montpellier, Centre National de la Recherche Scientifique, Institut de Recherche Pour le Dévelopement, Montpellier, France
- European Liquid Biopsy Society (ELBS), Hamburg, Germany
| | - Joanna Budna-Tukan
- Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland
- Department of Anatomy and Histology, Collegium Medicum, University of Zielona Gora, Zielona Gora, Poland
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Hassanzadeh-Barforoushi A, Tukova A, Nadalini A, Inglis DW, Chang-Hao Tsao S, Wang Y. Microfluidic-SERS Technologies for CTC: A Perspective on Clinical Translation. ACS APPLIED MATERIALS & INTERFACES 2024. [PMID: 38652011 DOI: 10.1021/acsami.4c01158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/25/2024]
Abstract
Enumeration and phenotypic profiling of circulating tumor cells (CTCs) provide critical information for clinical diagnosis and treatment monitoring in cancer. To achieve this goal, an integrated system is needed to efficiently isolate CTCs from patient samples and sensitively evaluate their phenotypes. Such integration would comprise a high-throughput single-cell processing unit for the isolation and manipulation of CTCs and a sensitive and multiplexed quantitation unit to detect clinically relevant signals from these cells. Surface-enhanced Raman scattering (SERS) has been used as an analytical method for molecular profiling and in vitro cancer diagnosis. More recently, its multiplexing capability and power to create distinct molecular signatures against their targets have garnered attention. Here, we share our insights into the combined power of microfluidics and SERS in realizing CTC isolation, enumeration, and detection from a clinical translation perspective. We highlight the key operational factors in CTC microfluidic processing and SERS detection from patient samples. We further discuss microfluidic-SERS integration and its clinical utility as a paradigm shift in clinical CTC-based cancer diagnosis and prognostication. Finally, we summarize the challenges and attempt to look forward to what lies ahead of us in potentially translating the technique into real clinical applications.
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Affiliation(s)
- Amin Hassanzadeh-Barforoushi
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Anastasiia Tukova
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Audrey Nadalini
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - David W Inglis
- School of Engineering, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
| | - Simon Chang-Hao Tsao
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
- Department of Surgery, Austin Health, University of Melbourne, Heidelberg, Victoria 3084, Australia
| | - Yuling Wang
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
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Wang H, Yang S, Chen L, Li Y, He P, Wang G, Dong H, Ma P, Ding G. Tumor diagnosis using carbon-based quantum dots: Detection based on the hallmarks of cancer. Bioact Mater 2024; 33:174-222. [PMID: 38034499 PMCID: PMC10684566 DOI: 10.1016/j.bioactmat.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/15/2023] [Accepted: 10/05/2023] [Indexed: 12/02/2023] Open
Abstract
Carbon-based quantum dots (CQDs) have been shown to have promising application value in tumor diagnosis. Their use, however, is severely hindered by the complicated nature of the nanostructures in the CQDs. Furthermore, it seems impossible to formulate the mechanisms involved using the inadequate theoretical frameworks that are currently available for CQDs. In this review, we re-consider the structure-property relationships of CQDs and summarize the current state of development of CQDs-based tumor diagnosis based on biological theories that are fully developed. The advantages and deficiencies of recent research on CQDs-based tumor diagnosis are thus explained in terms of the manifestation of nine essential changes in cell physiology. This review makes significant progress in addressing related problems encountered with other nanomaterials.
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Affiliation(s)
- Hang Wang
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- CAS Center for Excellence in Superconducting Electronics (CENSE), Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
| | - Siwei Yang
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
| | - Liangfeng Chen
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
| | - Yongqiang Li
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
| | - Peng He
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
| | - Gang Wang
- Department of Microelectronic Science and Engineering, School of Physical Science and Technology, Ningbo University, Ningbo, 315211, PR China
| | - Hui Dong
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- CAS Center for Excellence in Superconducting Electronics (CENSE), Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
| | - Peixiang Ma
- Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China
| | - Guqiao Ding
- National Key Laboratory of Materials for Integrated Circuit, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, PR China
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Anitha K, Posinasetty B, Naveen Kumari K, Chenchula S, Padmavathi R, Prakash S, Radhika C. Liquid biopsy for precision diagnostics and therapeutics. Clin Chim Acta 2024; 554:117746. [PMID: 38151071 DOI: 10.1016/j.cca.2023.117746] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 12/22/2023] [Accepted: 12/23/2023] [Indexed: 12/29/2023]
Abstract
Liquid biopsy (LB) has emerged as a highly promising and non-invasive diagnostic approach, particularly in the field of oncology, and has garnered interest in various medical disciplines. This technique involves the examination of biomolecules released into physiological fluids, such as urine samples, blood, and cerebrospinal fluid (CSF). The analysed biomolecules included circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free DNA (cfDNA), exosomes, and other cell-free components. In contrast to conventional tissue biopsies, LB provides minimally invasive diagnostics, offering invaluable insights into tumor characteristics, treatment response, and early disease detection. This Review explores the contemporary landscape of technologies and clinical applications in the realm of LB, with a particular emphasis on the isolation and analysis of ctDNA and/or cfDNA. Various methodologies have been employed, including droplet digital polymerase chain reaction (DDP), BEAMing (beads, emulsion, amplification, and magnetics), TAm-Seq (tagged-amplicon deep sequencing), CAPP-Seq (cancer personalized profiling by deep sequencing), WGBS-Seq (whole genome bisulfite sequencing), WES (whole exome sequencing), and WGS (whole-genome sequencing). Additionally, CTCs have been successfully isolated through biomarker-based cell capture, employing both positive and negative enrichment strategies based on diverse biophysical and other inherent properties. This approach also addresses challenges and limitations associated with liquid biopsy techniques, such as sensitivity, specificity, standardization and interpretability of findings. This review seeks to identify the current technologies used in liquid biopsy samples, emphasizing their significance in identifying tumor markers for cancer detection, prognosis, and treatment outcome monitoring.
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Affiliation(s)
- Kuttiappan Anitha
- Department of Pharmacology, School of Pharmacy and Technology Management (SPTM), SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed-to-University, Shirpur 425405, India
| | | | - K Naveen Kumari
- Sri Krishna Teja Pharmacy College, Tirupati, Andhra Pradesh 517502, India
| | | | - R Padmavathi
- SVS Medical College, Hyderabad, Telangana, India
| | - Satya Prakash
- All India Institute of Medical Sciences, Bhopal 462020, India
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Sharma YK, Gawande M, Reche A, Bardia MR. Circulating Tumor Cells in Oral Cancer. Cureus 2024; 16:e51684. [PMID: 38318575 PMCID: PMC10839405 DOI: 10.7759/cureus.51684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 01/04/2024] [Indexed: 02/07/2024] Open
Abstract
Till now, oral squamous cell carcinoma (OSCC) is graded as well-differentiated, moderately-differentiated, poorly-differentiated, and undifferentiated. However, this grading does not have a prediction of the prognosis of the patient. Also, prognosis impacts lymph node metastases, surgical margins, and vascular invasions (neural invasion, muscular invasion, salivary gland invasion). The prognosis of lymph node metastases is significant, which affects the survival of the patients which is 50%. So, a dependable blood marker is needed for prognosis in OSCC patients with loco-regional and distant recurrence. Some factors can be assisted only after surgery and invasive techniques to check the prognosis of the disease. Despite the ease of examining the oral cavity, there is no practical approach for non-invasive screening and detecting cancer. As it is abrupt to use such invasive procedures from time to time, there is a need for nonsurgical and reliable techniques to assess the progression of tumors. Also, frozen sections are helpful during the intraoperative procedure to evaluate the lymph node metastases. An increase in the number of tumor cells through blood is a significant event in disease metastases toward the peripheral blood. Oral health impact assessment instruments could aid in determining the quality of life, and their usage in the initial stages of oral carcinoma could help physicians choose the best treatment option for enhancing the quality of life.
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Affiliation(s)
- Yashika K Sharma
- Oral Pathology and Microbiology, Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Madhuri Gawande
- Oral Pathology and Microbiology, Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Amit Reche
- Public Health Dentistry, Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Muskan R Bardia
- Oral Pathology and Microbiology, Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Zhan Q, Liu B, Situ X, Luo Y, Fu T, Wang Y, Xie Z, Ren L, Zhu Y, He W, Ke Z. New insights into the correlations between circulating tumor cells and target organ metastasis. Signal Transduct Target Ther 2023; 8:465. [PMID: 38129401 PMCID: PMC10739776 DOI: 10.1038/s41392-023-01725-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 12/07/2023] [Accepted: 12/08/2023] [Indexed: 12/23/2023] Open
Abstract
Organ-specific metastasis is the primary cause of cancer patient death. The distant metastasis of tumor cells to specific organs depends on both the intrinsic characteristics of the tumor cells and extrinsic factors in their microenvironment. During an intermediate stage of metastasis, circulating tumor cells (CTCs) are released into the bloodstream from primary and metastatic tumors. CTCs harboring aggressive or metastatic features can extravasate to remote sites for continuous colonizing growth, leading to further lesions. In the past decade, numerous studies demonstrated that CTCs exhibited huge clinical value including predicting distant metastasis, assessing prognosis and monitoring treatment response et al. Furthermore, increasingly numerous experiments are dedicated to identifying the key molecules on or inside CTCs and exploring how they mediate CTC-related organ-specific metastasis. Based on the above molecules, more and more inhibitors are being developed to target CTCs and being utilized to completely clean CTCs, which should provide promising prospects to administer advanced tumor. Recently, the application of various nanomaterials and microfluidic technologies in CTCs enrichment technology has assisted to improve our deep insights into the phenotypic characteristics and biological functions of CTCs as a potential therapy target, which may pave the way for us to make practical clinical strategies. In the present review, we mainly focus on the role of CTCs being involved in targeted organ metastasis, especially the latest molecular mechanism research and clinical intervention strategies related to CTCs.
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Affiliation(s)
- Qinru Zhan
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Bixia Liu
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Xiaohua Situ
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Yuting Luo
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Tongze Fu
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Yanxia Wang
- Zhongshan School of Medicine, Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Zhongpeng Xie
- Zhongshan School of Medicine, Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Lijuan Ren
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China
| | - Ying Zhu
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China.
| | - Weiling He
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, 10065, USA.
- School of Medicine, Xiang'an Hospital of Xiamen University, Xiamen University, 361000, Xiamen, Fujian, P.R. China.
| | - Zunfu Ke
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China.
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, Guangdong, P.R. China.
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Guo S, Huang J, Li G, Chen W, Li Z, Lei J. The role of extracellular vesicles in circulating tumor cell-mediated distant metastasis. Mol Cancer 2023; 22:193. [PMID: 38037077 PMCID: PMC10688140 DOI: 10.1186/s12943-023-01909-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/23/2023] [Indexed: 12/02/2023] Open
Abstract
Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.
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Affiliation(s)
- Siyin Guo
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Jing Huang
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Genpeng Li
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Wenjie Chen
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Zhihui Li
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Jianyong Lei
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
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12
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Lim SH, Chua W, Ng W, Ip E, Marques TM, Tran NT, Gama-Carvalho M, Asghari R, Henderson C, Ma Y, de Souza P, Spring KJ. Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer. Cancers (Basel) 2023; 15:4184. [PMID: 37627212 PMCID: PMC10452825 DOI: 10.3390/cancers15164184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 08/08/2023] [Accepted: 08/18/2023] [Indexed: 08/27/2023] Open
Abstract
Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/- chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.
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Affiliation(s)
- Stephanie H. Lim
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
- Department of Medical Oncology, Macarthur Cancer Therapy Centre, Campbelltown, NSW 2560, Australia
- Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia
| | - Wei Chua
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
- Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia
- Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW 2170, Australia
| | - Weng Ng
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
- Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia
- Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW 2170, Australia
| | - Emilia Ip
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
- Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia
- Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW 2170, Australia
| | - Tania M. Marques
- BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal; (T.M.M.); (M.G.-C.)
| | - Nham T. Tran
- School Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW 2007, Australia;
| | - Margarida Gama-Carvalho
- BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal; (T.M.M.); (M.G.-C.)
| | - Ray Asghari
- Department of Medical Oncology, Bankstown Hospital, Bankstown, NSW 2200, Australia;
| | | | - Yafeng Ma
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
| | - Paul de Souza
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
- Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia
- School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia
- South West Sydney Clinical School, University of New South Wales, Liverpool, NSW 2170, Australia
| | - Kevin J. Spring
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (W.C.); (W.N.); (E.I.); (Y.M.); (P.d.S.)
- Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia
- South West Sydney Clinical School, University of New South Wales, Liverpool, NSW 2170, Australia
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13
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ALEMZADEH EFFAT, ALLAHQOLI LEILA, DEHGHAN HAMIDEH, MAZIDIMORADI AFROOZ, GHASEMPOUR ALIREZA, SALEHINIYA HAMID. Circulating tumor cells and circulating tumor DNA in breast cancer diagnosis and monitoring. Oncol Res 2023; 31:667-675. [PMID: 37547763 PMCID: PMC10398400 DOI: 10.32604/or.2023.028406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 05/19/2023] [Indexed: 08/08/2023] Open
Abstract
Liquid biopsy, including both circulating tumor cells and circulating tumor DNA, is becoming more popular as a diagnostic tool in the clinical management of breast cancer. Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance. Thus, these circulating markers serve as tools for cancer assessing and monitoring through a simple, non-invasive blood draw. However, despite several study results currently noting a potential clinical impact of ctDNA mutation tracking, the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it. This review focuses on understanding circulating tumor biomarkers, especially in breast cancer.
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Affiliation(s)
- EFFAT ALEMZADEH
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, 9717853577, Iran
| | - LEILA ALLAHQOLI
- Midwifery Department, Ministry of Health and Medical Education, Tehran, 9413933336, Iran
| | - HAMIDEH DEHGHAN
- Student Research Committee, Birjand University of Medical Sciences, Birjand, 9717853577, Iran
| | - AFROOZ MAZIDIMORADI
- Department of Health Assistant, Shiraz University of Medical Sciences, Shiraz, 7134814336, Iran
| | - ALIREZA GHASEMPOUR
- Student Research Committee, Birjand University of Medical Sciences, Birjand, 9717853577, Iran
| | - HAMID SALEHINIYA
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, 32048321, Iran
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14
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Shaik MR, Sagar PR, Shaik NA, Randhawa N. Liquid Biopsy in Hepatocellular Carcinoma: The Significance of Circulating Tumor Cells in Diagnosis, Prognosis, and Treatment Monitoring. Int J Mol Sci 2023; 24:10644. [PMID: 37445822 DOI: 10.3390/ijms241310644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/17/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor outcomes when diagnosed at an advanced stage. Current curative treatments are most effective in early-stage HCC, highlighting the importance of early diagnosis and intervention. However, existing diagnostic methods, such as radiological imaging, alpha-fetoprotein (AFP) testing, and biopsy, have limitations that hinder early diagnosis. AFP elevation is absent in a significant portion of tumors, and imaging may have low sensitivity for smaller tumors or in the presence of cirrhosis. Additionally, as our understanding of the molecular pathogenesis of HCC grows, there is an increasing need for molecular information about the tumors. Biopsy, although informative, is invasive and may not always be feasible depending on tumor location. In this context, liquid biopsy technology has emerged as a promising approach for early diagnosis, enabling molecular characterization and genetic profiling of tumors. This technique involves analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived exosomes. CTCs are cancer cells shed from the primary tumor or metastatic sites and circulate in the bloodstream. Their presence not only allows for early detection but also provides insights into tumor metastasis and recurrence. By detecting CTCs in peripheral blood, real-time tumor-related information at the DNA, RNA, and protein levels can be obtained. This article provides an overview of CTCs and explores their clinical significance for early detection, prognosis, treatment selection, and monitoring treatment response in HCC, citing relevant literature.
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Affiliation(s)
- Mohammed Rifat Shaik
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA
| | - Prem Raj Sagar
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA
| | - Nishat Anjum Shaik
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD 21201, USA
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15
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Ko SW, Yoon SB. Clinical implications and perspectives of portal venous circulating tumor cells in pancreatic cancer. World J Gastrointest Oncol 2023; 15:632-643. [PMID: 37123055 PMCID: PMC10134213 DOI: 10.4251/wjgo.v15.i4.632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/10/2023] [Accepted: 03/15/2023] [Indexed: 04/12/2023] Open
Abstract
Despite recent improvements in the diagnosis and treatment of pancreatic cancer (PC), clinical outcomes remain dismal. Moreover, there are no effective prognostic or predictive biomarkers or options beyond carbohydrate antigen 19-9 for personalized and precise treatment. Circulating tumor cells (CTCs), as a member of the liquid biopsy family, could be a promising biomarker; however, the rarity of CTCs in peripheral venous blood limits their clinical use. Because the first venous drainage of PC is portal circulation, the portal vein can be a more suitable location for the detection of CTCs. Endoscopic ultrasound-guided portal venous sampling of CTCs is both feasible and safe. Several studies have suggested that the detection rate and number of CTCs may be higher in the portal blood than in the peripheral blood. CTC counts in the portal blood are highly associated with hepatic metastasis, recurrence after surgery, and survival. The phenotypic and genotypic properties measured in the captured portal CTCs can help us to understand tumor heterogeneity and predict the prognosis of PC. Small sample sizes and heterogeneous CTC detection methods limit the studies to date. Therefore, a large number of prospective studies are needed to corroborate portal CTCs as a valid biomarker in PC.
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Affiliation(s)
- Sung Woo Ko
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, Seoul 03312, South Korea
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16
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Caputo V, Ciardiello F, Corte CMD, Martini G, Troiani T, Napolitano S. Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2023; 4:102-138. [PMID: 36937316 PMCID: PMC10017193 DOI: 10.37349/etat.2023.00125] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 11/13/2022] [Indexed: 03/06/2023] Open
Abstract
Liquid biopsy is a diagnostic repeatable test, which in last years has emerged as a powerful tool for profiling cancer genomes in real-time with minimal invasiveness and tailoring oncological decision-making. It analyzes different blood-circulating biomarkers and circulating tumor DNA (ctDNA) is the preferred one. Nevertheless, tissue biopsy remains the gold standard for molecular evaluation of solid tumors whereas liquid biopsy is a complementary tool in many different clinical settings, such as treatment selection, monitoring treatment response, cancer clonal evolution, prognostic evaluation, as well as the detection of early disease and minimal residual disease (MRD). A wide number of technologies have been developed with the aim of increasing their sensitivity and specificity with acceptable costs. Moreover, several preclinical and clinical studies have been conducted to better understand liquid biopsy clinical utility. Anyway, several issues are still a limitation of its use such as false positive and negative results, results interpretation, and standardization of the panel tests. Although there has been rapid development of the research in these fields and recent advances in the clinical setting, many clinical trials and studies are still needed to make liquid biopsy an instrument of clinical routine. This review provides an overview of the current and future clinical applications and opening questions of liquid biopsy in different oncological settings, with particular attention to ctDNA liquid biopsy.
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Affiliation(s)
- Vincenza Caputo
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Napoli, Italy
| | - Fortunato Ciardiello
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Napoli, Italy
| | - Carminia Maria Della Corte
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Napoli, Italy
| | - Giulia Martini
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Napoli, Italy
| | - Teresa Troiani
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Napoli, Italy
| | - Stefania Napolitano
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80131 Napoli, Italy
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17
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Calero-Castro FJ, Pereira S, Laga I, Villanueva P, Suárez-Artacho G, Cepeda-Franco C, de la Cruz-Ojeda P, Navarro-Villarán E, Dios-Barbeito S, Serrano MJ, Fresno C, Padillo-Ruiz J. Quantification and Characterization of CTCs and Clusters in Pancreatic Cancer by Means of the Hough Transform Algorithm. Int J Mol Sci 2023; 24:ijms24054278. [PMID: 36901704 PMCID: PMC10002258 DOI: 10.3390/ijms24054278] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/24/2023] Open
Abstract
Circulating Tumor Cells (CTCs) are considered a prognostic marker in pancreatic cancer. In this study we present a new approach for counting CTCs and CTC clusters in patients with pancreatic cancer using the IsofluxTM System with the Hough transform algorithm (Hough-IsofluxTM). The Hough-IsofluxTM approach is based on the counting of an array of pixels with a nucleus and cytokeratin expression excluding the CD45 signal. Total CTCs including free and CTC clusters were evaluated in healthy donor samples mixed with pancreatic cancer cells (PCCs) and in samples from patients with pancreatic ductal adenocarcinoma (PDAC). The IsofluxTM System with manual counting was used in a blinded manner by three technicians who used Manual-IsofluxTM as a reference. The accuracy of the Hough-IsofluxTM approach for detecting PCC based on counted events was 91.00% [84.50, 93.50] with a PCC recovery rate of 80.75 ± 16.41%. A high correlation between the Hough-IsofluxTM and Manual-IsofluxTM was observed for both free CTCs and for clusters in experimental PCC (R2 = 0.993 and R2 = 0.902 respectively). However, the correlation rate was better for free CTCs than for clusters in PDAC patient samples (R2 = 0.974 and R2 = 0.790 respectively). In conclusion, the Hough-IsofluxTM approach showed high accuracy for the detection of circulating pancreatic cancer cells. A better correlation rate was observed between Hough-IsofluxTM approach and with the Manual-IsofluxTM for isolated CTCs than for clusters in PDAC patient samples.
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Affiliation(s)
- Francisco José Calero-Castro
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Sheila Pereira
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Imán Laga
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Paula Villanueva
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Gonzalo Suárez-Artacho
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Carmen Cepeda-Franco
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Patricia de la Cruz-Ojeda
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Elena Navarro-Villarán
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | - Sandra Dios-Barbeito
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
| | | | - Cristóbal Fresno
- Health and Sciences Research Center, Health and Sciences Faculty, Anahuac University, Huixquilucan 52760, Mexico
- Correspondence: (C.F.); (J.P.-R.)
| | - Javier Padillo-Ruiz
- Department of General Surgery, Hospital University Virgen del Rocío/CSIC/University of Seville/IBiS, 41013 Seville, Spain
- Oncology Surgery, Cell Therapy, and Organ Transplantation Group, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain
- Correspondence: (C.F.); (J.P.-R.)
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18
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Zhao X, Qi Z, Gao Z, He H. High counting of circulating tumor cells in blood is not directly related to metastasis. Cytometry A 2023; 103:82-87. [PMID: 35912963 DOI: 10.1002/cyto.a.24672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 06/24/2022] [Accepted: 07/18/2022] [Indexed: 02/07/2023]
Abstract
Circulating tumor cells (CTCs) in blood flow have been believed as an essential biomarker of cancer. The technologies of in vitro and in vivo CTC enrichment and detection suggest although CTCs might play a role of "seed" in metastasis, only the minority of CTCs, probably in the form of CTC clusters, hold the potential to develop a tumor in organs. The detected amount of CTCs might be solely an indicator of tumor burden. To provide new insights into this argument, we take advantage of a safe drug to tune the pacemaker activity of a mouse tumor model to increase the heart rate for a period of time every day during the tumor development. We detect the CTCs in vivo by fast line scanning of a confocal microscope when the heart rate returns to the baseline and find the average CTC amount is significantly elevated in the drug-treated group but the metastases are even less than that of control. Our results imply the detected CTC counts in blood might not be directly related to metastasis.
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Affiliation(s)
- Xiaohui Zhao
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Ziang Qi
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Ziao Gao
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Hao He
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
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19
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Le MCN, Smith KA, Alipanah M, Chen K, Lagmay JP, Fan ZH. Microfluidics-Enabled Isolation and Single-Cell Analysis of Circulating Tumor Cells. Methods Mol Biol 2023; 2689:71-93. [PMID: 37430048 DOI: 10.1007/978-1-0716-3323-6_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/12/2023]
Abstract
Microfluidic platforms enable the enrichment and analysis of circulating tumor cells (CTCs), a potential biomarker for cancer diagnosis, prognosis, and theragnosis. Combined with immunocytochemistry/immunofluorescence (ICC/IF) assays for CTCs, microfluidics-enabled detection presents a unique opportunity to study tumor heterogeneity and predict treatment response, both of which can help cancer drug development. In this chapter, we detail the protocols and methods employed to fabricate and use a microfluidic device for the enrichment, detection, and analysis of single CTCs from the blood samples of sarcoma patients.
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Affiliation(s)
- Minh-Chau N Le
- Interdisciplinary Microsystems Group, Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, USA
| | - Kierstin A Smith
- Interdisciplinary Microsystems Group, Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, USA
| | - Morteza Alipanah
- Interdisciplinary Microsystems Group, Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, USA
| | - Kangfu Chen
- Interdisciplinary Microsystems Group, Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, USA
| | | | - Z Hugh Fan
- Interdisciplinary Microsystems Group, Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, USA.
- J. Crayton Pruitt Family Department of Biomedical Engineering, Gainesville, FL, USA.
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20
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Abstract
Over the last decade, molecular markers have become an integral part in the management of Central Nervous System (CNS) tumors. Somatic mutations that identify and prognosticate tumors are also detected in the bio-fluids especially the serum and CSF; the sampling of which is known as liquid biopsy (LB). These tumor-derived biomarkers include plasma circulating tumor cells (CTCs), cell-free DNA (cf/ctDNAs), circulating cell-free microRNAs (cfmiRNAs), circulating extracellular vesicles, or exosomes (EVs), proteins, and tumor educated platelets. Established in the management of other malignancies, liquid biopsy is becoming an important tool in the management of CNS tumors as well. This review presents a snapshot of the current state of LB research its potential and the possible pitfalls.
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Affiliation(s)
- Amitava Ray
- Senior Consultant Neurosurgeon, Department of Neurosciences, Apollo Health City and Apollo Secunderabad, Hyderabad 500089, Telangana, India
| | - Tarang K Vohra
- Consultant Neurosurgeon, Department of Neurosciences, Apollo Health City, Hyderabad 500089, Telangana, India
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21
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Jayasinghe R, Jayarajah U, Seneviratne S. Circulating Biomarkers in the Management of Breast Cancer. Biomark Med 2022. [DOI: 10.2174/9789815040463122010009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Circulating biomarkers have become a promising modality in the
management of many cancers. Similarly, in breast cancer, circulatory biomarkers are
useful, non-invasive methods in the diagnosis, prognostication, and evaluation of
response to treatment. Invasive surgical biopsies can be potentially replaced by “liquid
biopsy,” which involves analysing circulatory biomarkers that may reveal features of
primary and metastatic disease. Therefore, providing an insight into the cancer biology
can be utilised to monitor treatment response, treatment-induced adaptation and tumour
and disease progression through non-invasive means. The objective of this review is to
provide an overview of the current status of the circulating biomarkers highlighting
their promising impact on the management of patients with breast cancer.
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Affiliation(s)
- Ravindri Jayasinghe
- Faculty of Medicine, University of Colombo,Department of Surgery,Department of Surgery, Faculty of Medicine, University of Colombo, Colombo,Sri Lanka
| | - Umesh Jayarajah
- Faculty of Medicine, University of Colombo,Department of Surgery,Department of Surgery, Faculty of Medicine, University of Colombo, Colombo,Sri Lanka
| | - Sanjeewa Seneviratne
- Faculty of Medicine, University of Colombo,Department of Surgery,Department of Surgery, Faculty of Medicine, University of Colombo, Colombo,Sri Lanka
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22
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Edd JF, Mishra A, Smith KC, Kapur R, Maheswaran S, Haber DA, Toner M. Isolation of Circulating Tumor Cells. iScience 2022; 25:104696. [PMID: 35880043 PMCID: PMC9307519 DOI: 10.1016/j.isci.2022.104696] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Circulating tumor cells (CTCs) enter the vasculature from solid tumors and disseminate widely to initiate metastases. Mining the metastatic-enriched molecular signatures of CTCs before, during, and after treatment holds unique potential in personalized oncology. Their extreme rarity, however, requires isolation from large blood volumes at high yield and purity, yet they overlap leukocytes in size and other biophysical properties. Additionally, many CTCs lack EpCAM that underlies much of affinity-based capture, complicating their separation from blood. Here, we provide a comprehensive introduction of CTC isolation technology, by analyzing key separation modes and integrated isolation strategies. Attention is focused on recent progress in microfluidics, where an accelerating evolution is occurring in high-throughput sorting of cells along multiple dimensions.
Circulating tumor cells (CTCs) spread cancer through the bloodstream (metastasis) CTC-based liquid biopsy enables minimally invasive sampling of cancer cells in blood Their extreme rarity requires all CTC types to be enriched from large blood volumes CTC isolation technology is analyzed, with a focus on high-throughput microfluidics
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Affiliation(s)
- Jon F. Edd
- BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Avanish Mishra
- BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
| | | | - Ravi Kapur
- BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- BendBio, Inc., Sharon, MA 02067, USA
| | - Shyamala Maheswaran
- Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Daniel A. Haber
- Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
- Howard Hughes Medical Institute, Bethesda, MD 20815, USA
| | - Mehmet Toner
- BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
- Shriners Hospitals for Children, Boston, MA 02114, USA
- Corresponding author
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Roviello G, Lavacchi D, Antonuzzo L, Catalano M, Mini E. Liquid biopsy in colorectal cancer: No longer young, but not yet old. World J Gastroenterol 2022; 28:1503-1507. [PMID: 35582130 PMCID: PMC9048462 DOI: 10.3748/wjg.v28.i15.1503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 07/12/2021] [Accepted: 03/14/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers and the second leading cause of cancer-related deaths worldwide. The treatment strategy employed in CRC patients is becoming highly dependent on molecular characteristics present at diagnosis and during treatment. Liquid biopsy is an emerging field in the management of this cancer, and its relevance as a potential diagnostic, prognostic, monitoring, and therapeutic tool makes it a viable strategy in the clinical management of CRC patients. Liquid biopsy also has certain limitations, but these limitations seem to be at the reach of near-future technological development. In this letter, we focus on the clinical perspectives of liquid biopsy in CRC with particular regard to the various biomarkers recently identified that have been shown to be potentially useful in multiple aspects of early stage or metastatic CRC.
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Affiliation(s)
- Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze 50139, Italy
| | | | - Lorenzo Antonuzzo
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze 50134, Italy
| | - Martina Catalano
- School of Human Health Sciences, University of Florence, Florence 50134, Italy
| | - Enrico Mini
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze 50139, Italy
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Lone SN, Nisar S, Masoodi T, Singh M, Rizwan A, Hashem S, El-Rifai W, Bedognetti D, Batra SK, Haris M, Bhat AA, Macha MA. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. Mol Cancer 2022; 21:79. [PMID: 35303879 PMCID: PMC8932066 DOI: 10.1186/s12943-022-01543-7] [Citation(s) in RCA: 385] [Impact Index Per Article: 128.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/21/2022] [Indexed: 02/07/2023] Open
Abstract
Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.
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Affiliation(s)
- Saife N Lone
- Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, Jammu & Kashmir, India
| | - Sabah Nisar
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, PO BOX 26999, Doha, Qatar
| | - Tariq Masoodi
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, PO BOX 26999, Doha, Qatar
| | - Mayank Singh
- Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Arshi Rizwan
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Sheema Hashem
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, PO BOX 26999, Doha, Qatar
| | - Wael El-Rifai
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA
- Department of Veterans Affairs, Miami Healthcare System, Miami, FL, USA
| | - Davide Bedognetti
- Cancer Research Department, Research Branch, Sidra Medicince, Doha, Qatar
- Department of Internal Medicine and Medical Specialities, University of Genova, Genova, Italy
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, NE 68198, Omaha, USA
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center , Omaha, NE 68198, USA
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, University of Nebraska Medical Center, NE 68198, Omaha, USA
| | - Mohammad Haris
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, PO BOX 26999, Doha, Qatar
- Laboratory Animal Research Center, Qatar University, Doha, Qatar
- Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
| | - Ajaz A Bhat
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, PO BOX 26999, Doha, Qatar.
| | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, (IUST), 192122, Awantipora, Jammu & Kashmir, India.
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Hirahata T, ul Quraish R, Quraish AU, ul Quraish S, Naz M, Razzaq MA. Liquid Biopsy: A Distinctive Approach to the Diagnosis and Prognosis of Cancer. Cancer Inform 2022; 21:11769351221076062. [PMID: 35153470 PMCID: PMC8832574 DOI: 10.1177/11769351221076062] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/07/2022] [Indexed: 12/23/2022] Open
Abstract
Cancer is a leading cause of morbidity and mortality worldwide. Over the past decades, the concept of precision cancer medicine has emerged as a novel approach in the field of oncology that aims to tailor the most effective treatment options to each individual cancer patient based on the genetic profile of the tumor of each individual patient. Recently, tissue biopsy has become an essential part of cancer care and is widely used to characterize the tumor. However, tissue biopsy techniques face different challenges due to their invasiveness, cost, time, and adversity in potential sampling due to tissue heterogeneity. To overcome these issues, a non-invasive approach has developed, which is known as liquid biopsy. It is a simple, fast, and worthwhile technique based on the analysis of circulating tumor DNA (which is a fraction of cfDNA), circulating tumor cells (CTCs), and other tumor-derived material in blood plasma. This review provides an overview of the concept of liquid biopsy and briefly discusses the role of ctDNA and CTC analysis as tools for early diagnosis and prognosis of cancer. In this review, we also speculate on the advantages of liquid biopsy as opposed to tissue biopsy and postulate that liquid biopsy may be a comprehensive approach to overcome the current limitations associated with costly, invasive, and time-consuming tissue biopsy.
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Affiliation(s)
| | | | | | | | - Munazzah Naz
- Hirahata Gene Therapy Laboratory, HIC Clinic, Tokyo, Japan
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Yan TB, Huang JQ, Huang SY, Ahir BK, Li LM, Mo ZN, Zhong JH. Advances in the Detection of Pancreatic Cancer Through Liquid Biopsy. Front Oncol 2021; 11:801173. [PMID: 34993149 PMCID: PMC8726483 DOI: 10.3389/fonc.2021.801173] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/06/2021] [Indexed: 01/27/2023] Open
Abstract
Pancreatic cancer refers to the development of malignant tumors in the pancreas: it is associated with high mortality rates and mostly goes undetected in its early stages for lack of symptoms. Currently, surgical treatment is the only effective way to improve the survival of pancreatic cancer patients. Therefore, it is crucial to diagnose the disease as early as possible in order to improve the survival rate of patients with pancreatic cancer. Liquid biopsy is a unique in vitro diagnostic technique offering the advantage of earlier detection of tumors. Although liquid biopsies have shown promise for screening for certain cancers, whether they are effective for early diagnosis of pancreatic cancer is unclear. Therefore, we reviewed relevant literature indexed in PubMed and collated updates and information on advances in the field of liquid biopsy with respect to the early diagnosis of pancreatic cancer.
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Affiliation(s)
- Tian-Bao Yan
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Center for Genomics and Personalized Medicine, Guangxi Key Laboratory for Genomics and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomics and Personalized Medicine, Guangxi Medical University, Nanning, China
| | - Jia-Qi Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Center for Genomics and Personalized Medicine, Guangxi Key Laboratory for Genomics and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomics and Personalized Medicine, Guangxi Medical University, Nanning, China
| | - Shi-Yun Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Center for Genomics and Personalized Medicine, Guangxi Key Laboratory for Genomics and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomics and Personalized Medicine, Guangxi Medical University, Nanning, China
| | - Bhavesh K. Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Long-Man Li
- Center for Genomics and Personalized Medicine, Guangxi Key Laboratory for Genomics and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomics and Personalized Medicine, Guangxi Medical University, Nanning, China
| | - Zeng-Nan Mo
- Center for Genomics and Personalized Medicine, Guangxi Key Laboratory for Genomics and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomics and Personalized Medicine, Guangxi Medical University, Nanning, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
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Espejo-Cruz ML, González-Rubio S, Zamora-Olaya J, Amado-Torres V, Alejandre R, Sánchez-Frías M, Ciria R, De la Mata M, Rodríguez-Perálvarez M, Ferrín G. Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal. Int J Mol Sci 2021; 22:13073. [PMID: 34884878 PMCID: PMC8657934 DOI: 10.3390/ijms222313073] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/27/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and a major cause of cancer-related death worldwide. There is no ideal biomarker allowing early diagnosis of HCC and tumor surveillance in patients receiving therapy. Liquid biopsy, and particularly circulating tumor cells (CTCs), have emerged as a useful tool for diagnosis and monitoring therapeutic responses in different tumors. In the present manuscript, we evaluate the current evidence supporting the quantitative and qualitative assessment of CTCs as potential biomarkers of HCC, as well as technical aspects related to isolation, identification, and classification of CTCs. Although the dynamic assessment of CTCs in patients with HCC may aid the decision-making process, there are still many uncertainties and technical caveats to be solved before this methodology has a true impact on clinical practice guidelines. More studies are needed to identify the optimal combination of surface markers, to increase the efficiency of ex-vivo expansion of CTCs, or even to target CTCs as a potential therapeutic strategy to prevent HCC recurrence after surgery or to hamper tumor progression and extrahepatic spreading.
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Affiliation(s)
- María Lola Espejo-Cruz
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
| | - Sandra González-Rubio
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
| | - Javier Zamora-Olaya
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
| | - Víctor Amado-Torres
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
| | - Rafael Alejandre
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
| | - Marina Sánchez-Frías
- Department of Pathology, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain;
| | - Rubén Ciria
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatobiliary Surgery and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - Manuel De la Mata
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Manuel Rodríguez-Perálvarez
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Gustavo Ferrín
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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Jiang AM, Zheng HR, Liu N, Zhao R, Ma YY, Bai SH, Tian T, Liang X, Ruan ZP, Fu X, Yao Y. Assessment of the Clinical Utility of Circulating Tumor Cells at Different Time Points in Predicting Prognosis of Patients With Small Cell Lung Cancer: A Meta-Analysis. Cancer Control 2021; 28:10732748211050581. [PMID: 34654345 PMCID: PMC8521771 DOI: 10.1177/10732748211050581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Objectives Numerous studies have elucidated that circulating tumor cells (CTCs) have significant prognostic value in various solid tumors. However, the prognostic value of CTCs in small cell lung cancer (SCLC) remains controversial. The current study was performed to investigate the prognostic significance of different time points of CTCs in SCLC. Methods PubMed, EMBASE, Web of Science, and Cochrane Library databases were retrieved for eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the association between CTCs level and overall survival (OS) and progression-free survival (PFS) in SCLC. Furthermore, subgroup analyses, sensitivity analysis, Begg’s and Egger’s tests were also conducted. Results Sixteen cohort studies with 1103 participants were eligible for this meta-analysis. Our results revealed that higher pretreatment CTCs level was significantly correlated with worse OS in SCLC no matter CellSearch (HR, 2.95; 95%CI, 1.56-5.58; P = .001) or other methods (HR, 2.37; 95%CI, 1.13-4.99; P = .023) was used to detect CTCs. Higher pretreatment CTCs status detected by CellSearch was associated with shorter PFS (HR, 3.75; 95%CI, 2.52-5.57; P < .001), while there was no significant association when other methods were adopted to CTC detection (HR, 2.04; 95%CI, .73-5.68; P = .172). Likewise, we observed that higher post-therapy CTCs level detected by both CellSearch (HR, 2.99; 95%CI, 1.51-5.93; P = .002) and other methods (HR, 4.79; 95%CI, 2.03-11.32; P < .001) was significantly correlated with decreased OS in SCLC. However, higher post-therapy CTCs count detected by CellSearch was not correlated with worse PFS (HR, 1.80; 95%CI, .83-3.90; P = .135). Sensitivity analysis demonstrated that the pooled data were still stable after eliminating studies one by one. However, significant publication bias was observed between pretreatment CTCs level detected by CellSearch and OS of SCLC. Conclusion Dynamic monitoring of CTCs level could be a non-invasive and effective tool to predict the disease progression and prognosis in patients with SCLC.
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Affiliation(s)
- Ai-Min Jiang
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Hao-Ran Zheng
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Na Liu
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Rui Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, 540681Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Yu-Yan Ma
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Shu-Heng Bai
- Department of Radiotherapy Oncology, 162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Tao Tian
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Xuan Liang
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Zhi-Ping Ruan
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Xiao Fu
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yu Yao
- Department of Medical Oncology,162798The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
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Wang J, Yu X, Peng H, Lu Y, Li S, Shi Q, Liu J, Dong H, Katanaev V, Jia L. Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:300. [PMID: 34556175 PMCID: PMC8461875 DOI: 10.1186/s13046-021-02104-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 09/15/2021] [Indexed: 12/01/2022]
Abstract
Background The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. Methods Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17β-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. Results Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17β-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. Conclusions The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.
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Affiliation(s)
- Jie Wang
- College of Materials and Chemical Engineering, Minjiang University, 350108, Fuzhou, China
| | - Xiaobo Yu
- Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, 350108, Fuzhou, P.R. China
| | - Huayi Peng
- Fujian Provincial Key Laboratory of Inspection and Quarantine Technology Research/ Technology Center of Fuzhou Customs, 350108, Fuzhou, China
| | - Yusheng Lu
- College of Materials and Chemical Engineering, Minjiang University, 350108, Fuzhou, China
| | - Shuhui Li
- Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, 350108, Fuzhou, P.R. China
| | - Qing Shi
- Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, 350108, Fuzhou, P.R. China
| | - Jian Liu
- Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, 350108, Fuzhou, P.R. China
| | - Haiyan Dong
- Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, 350108, Fuzhou, China
| | - Vladimir Katanaev
- College of Materials and Chemical Engineering, Minjiang University, 350108, Fuzhou, China.,Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Lee Jia
- College of Materials and Chemical Engineering, Minjiang University, 350108, Fuzhou, China.
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Yang W, Fan L, Guo Z, Wu H, Chen J, Liu C, Yan Y, Ding S. Reversible capturing and voltammetric determination of circulating tumor cells using two-dimensional nanozyme based on PdMo decorated with gold nanoparticles and aptamer. Mikrochim Acta 2021; 188:319. [PMID: 34476628 DOI: 10.1007/s00604-021-04927-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 07/04/2021] [Indexed: 12/25/2022]
Abstract
A novel cytosensor was constructed for the ultrasensitive detection and nondestructive release of circulating tumor cells (CTCs) by combining Au nanoparticles-loaded two-dimensional bimetallic PdMo (2D Au@PdMo) nanozymes and electrochemical reductive desorption. The 2D Au@PdMo nanozymes possessed high-efficiency peroxidase-like activity and were assembled with an aptamer composed of a thiol-modified epithelial specific cell adhesion molecule (EpCAM) to strengthen CTCs adhesion. Moreover, the electrode surface was decorated with highly fractal Au nanostructures (HFAuNSs) composites due to the similarity in fractal nanostructure with the CTCs membrane to enhance the CTCs anchoring efficiency and release capability. The captured CTCs could be further efficiently dissociated and nondestructively released from the modified electrodes upon electrochemical reductive desorption. The designed cytosensor showed an excellent analytical performance, with a wide linear range from 2 to 1 × 105 cells mL-1 and low limit of detection (LOD) of 2 cells mL-1 (S/N = 3) at the working potential in the range -0.6 to 0.2 V. A satisfactory CTCs release reaching a range of 93.7-97.4% with acceptable RSD from 3.55 to 6.41% and good cell viability was obtained. Thus, the developed cytosensor might provide a potential alternative to perform CTC-based liquid biopsies, with promising applications in early diagnosis of tumors. Preparation and mechanism of desorption of the cytosensor based on 2D Au@PdMo nanozymes and electrochemical reductive desorption for the detection and release of CTCs. A Preparation procedure of the Apt/Au@PbMo bioconjugates. B Fabrication process of the sandwich-type cytosensor. C Electrochemical signal produced by the Au@PdMo nanozymes. D Mechanism of electrochemical reductive desorption for CTCs release.
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Affiliation(s)
- Wei Yang
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.,Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China
| | - Lu Fan
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.,NMI Natural and Medical Sciences Institute, University of Tübingen, 72770, Reutlingen, Germany
| | - Zhen Guo
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Haiping Wu
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Junman Chen
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Changjin Liu
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yurong Yan
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
| | - Shijia Ding
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
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Bridging the Gaps between Circulating Tumor Cells and DNA Methylation in Prostate Cancer. Cancers (Basel) 2021; 13:cancers13164209. [PMID: 34439363 PMCID: PMC8391503 DOI: 10.3390/cancers13164209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/14/2021] [Accepted: 08/18/2021] [Indexed: 01/09/2023] Open
Abstract
Prostate cancer is the second most common male malignancy, with a highly variable clinical presentation and outcome. Therefore, diagnosis, prognostication, and management remain a challenge, as available clinical, imaging, and pathological parameters provide limited risk assessment. Thus, many biomarkers are under study to fill this critical gap, some of them based on epigenetic aberrations that might be detected in liquid biopsies. Herein, we provide a critical review of published data on the usefulness of DNA methylation and circulating tumor cells in diagnosis and treatment decisions in cases of prostate cancer, underlining key aspects and discussing the importance of these advances to the improvement of the management of prostate cancer patients. Using minimally invasive blood tests, the detection of highly specific biomarkers might be crucial for making therapeutic decisions, determining response to specific treatments, and allowing early diagnosis.
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Strati A, Zavridou M, Kallergi G, Politaki E, Kuske A, Gorges TM, Riethdorf S, Joosse SA, Koch C, Bohnen AL, Mueller V, Koutsodontis G, Kontopodis E, Poulakaki N, Psyrri A, Mavroudis D, Georgoulias V, Pantel K, Lianidou ES. A Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer. Clin Chem 2021; 67:1395-1405. [PMID: 34322698 DOI: 10.1093/clinchem/hvab099] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/13/2021] [Indexed: 11/12/2022]
Abstract
BACKGROUND Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa). METHODS In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining. RESULTS All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection. CONCLUSIONS In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs.
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Affiliation(s)
- Areti Strati
- Department of Chemistry, Analysis of Circulating Tumor Cells Laboratory, University of Athens, Greece
| | - Martha Zavridou
- Department of Chemistry, Analysis of Circulating Tumor Cells Laboratory, University of Athens, Greece
| | - Galatea Kallergi
- Laboratory of Τumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.,Division of Genetics, Cell, and Developmental Biology, Department of Biology, University of Patras, Patras, Greece
| | - Eleni Politaki
- Laboratory of Τumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - Andra Kuske
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tobias M Gorges
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sabine Riethdorf
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Simon A Joosse
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Koch
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anna-Lena Bohnen
- Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Volkmar Mueller
- Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - George Koutsodontis
- Oncology Unit, Second Department of Internal Medicine, Attikon University Hospital, Haidari, Greece
| | - Emmanouil Kontopodis
- Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
| | | | - Amanda Psyrri
- Oncology Unit, Second Department of Internal Medicine, Attikon University Hospital, Haidari, Greece
| | - Dimitris Mavroudis
- Laboratory of Τumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.,Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
| | - Vasilis Georgoulias
- Laboratory of Τumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - Klaus Pantel
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Evi S Lianidou
- Department of Chemistry, Analysis of Circulating Tumor Cells Laboratory, University of Athens, Greece
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Basso U, Facchinetti A, Rossi E, Maruzzo M, Conteduca V, Aieta M, Massari F, Fraccon AP, Mucciarini C, Sava T, Santoni M, Pegoraro C, Durante E, Nicodemo M, Perin A, Bearz A, Gatti C, Fiduccia P, Diminutto A, Barile C, De Giorgi U, Zamarchi R, Zagonel V. Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial. Oncologist 2021; 26:740-750. [PMID: 34077597 DOI: 10.1002/onco.13842] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 03/25/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). MATERIALS AND METHODS We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. RESULTS One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. CONCLUSION We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. IMPLICATIONS FOR PRACTICE This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.
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Affiliation(s)
- Umberto Basso
- Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
| | - Antonella Facchinetti
- Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.,Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Elisabetta Rossi
- Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.,Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Marco Maruzzo
- Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
| | - Vincenza Conteduca
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Michele Aieta
- Department of Onco-Hematology, Division of Medical Oncology, Centro di Riferimento Oncologico della Basilicata IRCCS, Rionero in Vulture, Italy
| | - Francesco Massari
- Department of Medical Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.,Medical Oncology, IRCCS Azienda Ospedaliera Universitaria, Bologna, Italy
| | - Anna Paola Fraccon
- Medical Oncology, Ospedale P. Pederzoli, Peschiera Del Garda, Peschiera Del Garda (VR), Italy
| | - Claudia Mucciarini
- Medical Oncology Unit, Ramazzini Hospital, Carpi-AUSL Modena, Modena, Italy
| | - Teodoro Sava
- Medical Oncology, Ospedale Borgo Trento, Verona, Italy
| | - Matteo Santoni
- Medical Oncology, Polytechnic University of the Marche Region, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy
| | - Cristina Pegoraro
- Medical Oncology Ospedale di Montecchio Maggiore, Azienda ULSS 8 Berica, Berica, Italy
| | - Emilia Durante
- Department of Medical Oncology, Ospedale di Legnago, Azienda ULSS 9 Scaligera, Scaligera, Italy
| | - Maurizio Nicodemo
- Department of Medical Oncology, Sacro Cuore - Don Calabria Hospital, Negrar, Italy
| | - Alessandra Perin
- Medical Oncology, Polo Unico Ospedale Santorso, Santorso, Azienda ULSS 7 Pedemontana, Pedemontana, Italy
| | - Alessandra Bearz
- Department of Medical Oncology, Centro Riferimento Oncologico CRO IRCCS, Aviano, Italy
| | - Carlo Gatti
- Medical Oncology, Ospedale di Chioggia, Azienda ULSS 3 Serenissima, Chioggia, Italy
| | - Pasquale Fiduccia
- Clinical Research Unit, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
| | - Alberto Diminutto
- Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
| | - Carmen Barile
- Medical Oncology, Ospedale di Rovigo, Azienda ULSS 5 Polesana, Rovigo, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy
| | - Rita Zamarchi
- Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
| | - Vittorina Zagonel
- Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
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Shen S, Yi Z, Li X, Xie S, Jin M, Zhou G, Yan Z, Shui L. Flow-Field-Assisted Dielectrophoretic Microchips for High-Efficiency Sheathless Particle/Cell Separation with Dual Mode. Anal Chem 2021; 93:7606-7615. [PMID: 34003009 DOI: 10.1021/acs.analchem.1c00018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Prefocusing of cell mixtures through sheath flow is a common technique used for continuous and high-efficiency dielectrophoretic (DEP) cell separation. However, it usually limits the separation flow velocity and requires a complex multichannel fluid control system that hinders the integration of a DEP separator with other microfluidic functionalities for comprehensive biomedical applications. Here, we propose and develop a high-efficiency, sheathless particle/cell separation method without prefocusing based on flow-field-assisted DEP by combining the effects of AC electric field (E-field) and flow field (F-field). A hollow lemon-shaped electrode array is designed to generate a long-range E-field gradient in the microchannel, which can effectively induce lateral displacements of particles/cells in a continuous flow. A series of arc-shaped protrusion structures is designed along the microchannel to form a F-field, which can effectively guide the particles/cells toward the targeted E-field region without prefocusing. By tuning the E-field, two distinct modes can be realized and switched in one single device, including the sheathless separation (ShLS) and the adjustable particle mixing ratio (AMR) modes. In the ShLS mode, we have achieved the continuous separation of breast cancer cells from erythrocytes with a recovery rate of 95.5% and the separation of polystyrene particles from yeast cells with a purity of 97.1% at flow velocities over 2.59 mm/s in a 2 cm channel under optimized conditions. The AMR mode provides a strategy for controlling the mixing ratio of different particles/cells as a well-defined pretreatment method for biomedical research studies. The proposed microchip is easy to use and displays high versatility for biological and medical applications.
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Affiliation(s)
- Shitao Shen
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
| | - Zichuan Yi
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China.,College of Electron and Information, University of Electronic Science and Technology of China, Zhongshan Institute, Zhongshan 528402, China
| | - Xing Li
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
| | - Shuting Xie
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
| | - Mingliang Jin
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
| | - Guofu Zhou
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
| | - Zhibin Yan
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
| | - Lingling Shui
- International Joint Laboratory of Optofluidic Technology and System, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics and School of Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006, China
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Smit DJ, Pantel K, Jücker M. Circulating tumor cells as a promising target for individualized drug susceptibility tests in cancer therapy. Biochem Pharmacol 2021; 188:114589. [PMID: 33932470 DOI: 10.1016/j.bcp.2021.114589] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/24/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023]
Abstract
Circulating tumor cells (CTCs) play a crucial role in metastasis and became an emerging topic in today's cancer research. In addition, the analysis of CTCs in liquid biopsies will be a valuable tool for prognosis prediction and real time therapy monitoring. The characterization of CTCs may open up a new field of treatment strategy to prevent metastasis or maintain a stable disease. In 2013, the first cell cultures of CTCs have been established in vitro. Additionally, functional studies have been successfully performed over the last years. Meanwhile, more than 300 short-term CTC cultures and 42 long-term CTC cultures from a variety of tumor entities have been described. More than 45 inhibitors have already been tested for their efficacy to target CTCs in several studies in vitro as well as in xenograft mouse models in vivo. Here, we summarize the currently available data of these inhibition experiments and their effects in targeting CTCs. The results suggest that CTCs may be useful for individualized drug susceptibility testing.
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Affiliation(s)
- Daniel J Smit
- Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Klaus Pantel
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Manfred Jücker
- Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
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Molodysky E, Grant R. Person-to-Person Cancer Transmission via Allogenic Blood Transfusion. Asian Pac J Cancer Prev 2021; 22:641-649. [PMID: 33773525 PMCID: PMC8286663 DOI: 10.31557/apjcp.2021.22.3.641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 11/03/2021] [Indexed: 11/25/2022] Open
Abstract
Despite the recognized capability of Circulating Tumor Cells (CTCs) to seed tumors, allogenic blood transfusions are not presently screened for the presence of CTCs. Previous research has examined blood transfusions and the associated risk of cancer recurrence, but not cancer of unknown primary (CUP) occurrence. The Hypothesis explored in this paper proposes that there is potential for cancers to be transmitted from donor-to-patient via CTCs in either blood transfusions or organ transplants or both. This proposed haematogenic tumor transmission will be discussed in relation to two scenarios involving the introduction of donor-derived CTC's from allogeneic blood transfusions into either known cancer surgery patients or into non-cancer patients. The source of CTCs arises either from the donor with a 'clinically dormant cancer' or a 'pre-clinical cancer' existing as yet undiagnosed, in the donor. Given the significant number of allogenic blood transfusions that occur worldwide on a yearly basis, allogenic blood transfusions have the potential to expose a substantial number of non-cancer recipients to the transmission of CTCs and associated tumor risk. This risk is greatly amplified in the low-income nations where the blood collection and processing protocols, including exclusion and screening criteria are less stringent than those in high-income countries.
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Affiliation(s)
- Eugen Molodysky
- Sydney Medical School, University of Sydney, Sydney, Australia.
| | - Ross Grant
- Sydney Medical School, University of Sydney, Sydney, Australia.
- School of Medical Sciences, University of NSW, Sydney, Australia.
- Australasian Research Institute, Sydney Adventist Hospital, Wahroonga, Sydney Australia.
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37
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Ahn JC, Teng PC, Chen PJ, Posadas E, Tseng HR, Lu SC, Yang JD. Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis, Prognostication, and Therapeutic Monitoring in Hepatocellular Carcinoma. Hepatology 2021; 73:422-436. [PMID: 32017145 PMCID: PMC8183673 DOI: 10.1002/hep.31165] [Citation(s) in RCA: 235] [Impact Index Per Article: 58.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 01/28/2020] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is among the leading causes of worldwide cancer-related morbidity and mortality. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced stage when there is no effective treatment to achieve the long term survival of patients. Currently available tests such as alpha-fetoprotein have limited accuracy as a diagnostic or prognostic biomarker for HCC. Liver biopsy provides tissue that can reveal tumor biology but it is not used routinely due to its invasiveness and risk of tumor seeding, especially in early-stage patients. Liver biopsy is also limited in revealing comprehensive tumor biology due to intratumoral heterogeneity. There is a clear need for new biomarkers to improve HCC detection, prognostication, prediction of treatment response, and disease monitoring with treatment. Liquid biopsy could be an effective method of early detection and management of HCC. Circulating tumor cells (CTCs) are cancer cells in circulation derived from the original tumor or metastatic foci, and their measurement by liquid biopsy represents a great potential in facilitating the implementation of precision medicine in patients with HCC. CTCs can be detected by a simple peripheral blood draw and potentially show global features of tumor characteristics. Various CTC detection platforms using immunoaffinity and biophysical properties have been developed to identify and capture CTCs with high efficiency. Quantitative abundance of CTCs, as well as biological characteristics and genomic heterogeneity among the CTCs, can predict disease prognosis and response to therapy in patients with HCC. This review article will discuss the currently available technologies for CTC detection and isolation, their utility in the clinical management of HCC patients, their limitations, and future directions of research.
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Affiliation(s)
- Joseph C Ahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55904, United States
| | - Pai-Chi Teng
- Urologic Oncology Program and Uro-Oncology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Pin-Jung Chen
- Department of Molecular and Medical Pharmacology, California NanoSystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, CA 90095, United States
| | - Edwin Posadas
- Urologic Oncology Program and Uro-Oncology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States,Translational Oncology Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States,Division of Hematology/Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Hsian-Rong Tseng
- Department of Molecular and Medical Pharmacology, California NanoSystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, CA 90095, United States
| | - Shelly C. Lu
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States,Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Ju Dong Yang
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States,Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States,Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
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38
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Rossi E, Aieta M, Tartarone A, Pezzuto A, Facchinetti A, Santini D, Ulivi P, Ludovini V, Possidente L, Fiduccia P, Minicuci N, Zamarchi R. A fully automated assay to detect the expression of pan-cytokeratins and of EML4-ALK fusion protein in circulating tumour cells (CTCs) predicts outcome of non-small cell lung cancer (NSCLC) patients. Transl Lung Cancer Res 2021; 10:80-92. [PMID: 33569295 PMCID: PMC7867748 DOI: 10.21037/tlcr-20-855] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background In advanced non-small cell lung cancer (NSCLC) a recent meta-analysis confirms circulating tumour cells (CTCs) as an independent prognostic indicator of progression-free survival (PFS) and overall survival (OS). However, further investigations are necessary to predict and dynamically monitor the therapy in NSCLC patients using CTCs. To this aim, we combined the classical standard assay (SA) with an expanded cytokeratins profile (EA) and quantified the expression of EML4-ALK fusion protein in CTCs. Methods The CellSearch (CS) platform—first marked in vitro diagnostic use (IVD) from Food and Drug Administration (FDA), and “gold standard” for quantifying CTCs - detects EpCAM and cytokeratins (CKs) 8, 18, and 19. Since NSCLC shows different CKs profile, we customized the SA, to recognize CK 4, 5, 6, 7, 8, 10, 13, 14, 18, and 19 (EA). Using both assays we designed a prospective, multi-center study, primarily aimed to enumerate CTCs in advanced NSCLC. Secondarily, we developed an integration of the EA to quantify the expression of EML4-ALK fusion protein in CTCs, and correlated them with PFS and OS. Results EA identified a significantly much more number of CTC-positive patients (115 out of 180) than SA (103 out of 192; Chi-square =4.0179, with 1 degrees of freedom, P=0.04502). Similar to SA, EA levels were still associated with patient’ outcomes. Furthermore, the expression of EML4-ALK on CTCs allowed stratifying NSCLC patients according to a statistically significant difference in PFS. Conclusions We proposed here two novel automated tests, to characterize the expression of specific molecules on CTCs. We demonstrated that these integrated assays are robust and actionable in prospective clinical studies, and in the future could allow clinicians to improve both choice and length of treatment in individual NSCLC patient.
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Affiliation(s)
- Elisabetta Rossi
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.,Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | | | | | - Aldo Pezzuto
- Department of Cardiopulmonary and Vascular Science, S. Andrea Hospital-Sapienza University, Roma, Italy
| | - Antonella Facchinetti
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.,Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Daniele Santini
- Medical Oncology Unit, Campus Bio-Medico University, Rome, Italy
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
| | - Vienna Ludovini
- Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy
| | | | | | | | - Rita Zamarchi
- Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
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Wu S, Pan Y, Mao Y, Chen Y, He Y. Current progress and mechanisms of bone metastasis in lung cancer: a narrative review. Transl Lung Cancer Res 2021; 10:439-451. [PMID: 33569325 PMCID: PMC7867745 DOI: 10.21037/tlcr-20-835] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and how can we treat it. Here, we reviewed the process, possible mechanisms, diagnosis methods and current treatment of bone metastasis in lung cancer. We divided the process of bone metastasis in lung cancer into three steps: tumor invasion, tumor cell migration and invasion in bone tissue. It may be influenced by genetic factors, microenvironment and other adhesion-related factors. Imaging examination, laboratory examination, and pathological examination are used to diagnose lung cancer metastasis to bone. Surgery, radiotherapy, targeted therapy, bisphosphonate, radiation therapy and chemotherapy are the common clinical treatment methods currently. We also found some problems remained to be solved. For example, drugs for skeletal related events mainly target on osteoclasts at present, which increase the ratio of patients in osteoporosis and fractures in the long term. In all, this review provides the direction for future research on bone metastasis in lung cancer.
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Affiliation(s)
- Shengyu Wu
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.,Medical School, Tongji University, Shanghai, China
| | - Yue Pan
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.,Medical School, Tongji University, Shanghai, China
| | - Yanyu Mao
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.,Medical School, Tongji University, Shanghai, China
| | - Yu Chen
- Spine Center, Orthopedic department, Shanghai Changzheng Hospital, Shanghai, China
| | - Yayi He
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
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Bersani F, Morena D, Picca F, Morotti A, Tabbò F, Bironzo P, Righi L, Taulli R. Future perspectives from lung cancer pre-clinical models: new treatments are coming? Transl Lung Cancer Res 2020; 9:2629-2644. [PMID: 33489823 PMCID: PMC7815341 DOI: 10.21037/tlcr-20-189] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Lung cancer currently stands out as both the most common and the most lethal type of cancer, the latter feature being partly explained by the fact that the majority of lung cancer patients already display advanced disease at the time of diagnosis. In recent years, the development of specific tyrosine kinase inhibitors (TKI) for the therapeutic benefit of patients harboring certain molecular aberrations and the introduction of prospective molecular profiling in the clinical practice have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, the identification of the best strategies to enhance treatment effectiveness and to avoid the critical phenomenon of drug tolerance and acquired resistance in patients with lung cancer still remains an unmet medical need. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two complementary approaches to define tumor heterogeneity and clonal evolution in a non-invasive manner and to perform functional studies on metastatic cells. Finally, the recent discovery that the tumor microenvironment architecture can be faithfully recapitulated in vitro represents a novel pre-clinical frontier with the potential to optimize more effective immunology-based precision therapies that could rapidly move forward to the clinic.
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Affiliation(s)
- Francesca Bersani
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
| | - Deborah Morena
- Department of Oncology, University of Torino, 10043 Orbassano, Italy.,Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, 10126 Torino, Italy
| | - Francesca Picca
- Department of Oncology, University of Torino, 10043 Orbassano, Italy.,Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, 10126 Torino, Italy
| | - Alessandro Morotti
- Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Italy
| | - Fabrizio Tabbò
- Thoracic Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital, University of Torino, 10043 Orbassano, Italy
| | - Paolo Bironzo
- Department of Oncology, University of Torino, 10043 Orbassano, Italy.,Thoracic Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital, University of Torino, 10043 Orbassano, Italy
| | - Luisella Righi
- Department of Oncology, University of Torino, 10043 Orbassano, Italy.,Pathology Unit, Department of Oncology at San Luigi Hospital, University of Torino, 10043 Orbassano, Italy
| | - Riccardo Taulli
- Department of Oncology, University of Torino, 10043 Orbassano, Italy.,Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, 10126 Torino, Italy
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Abstract
OBJECTIVES There is a significant unmet need for a blood test with adequate sensitivity to detect colorectal cancer (CRC) and adenomas. We describe a novel circulating tumor cell (CTC) platform to capture colorectal epithelial cells associated with CRC and adenomas. METHODS Blood was collected from 667 Taiwanese adults from 2012 to 2018 before a colonoscopy. The study population included healthy control subjects, patients with adenomas, and those with stage I-IV CRC. CTCs were isolated from the blood using the CellMax platform. The isolated cells were enumerated, and an algorithm was used to determine the likelihood of detecting adenoma or CRC. Nominal and ordinal logistic regression demonstrated that CTC counts could identify adenomas and CRC, including CRC stage. RESULTS The CellMax test demonstrated a significant association between CTC counts and worsening disease status (Cuzick's P value < 0.0001) with respect to the adenoma-carcinoma sequence. The test showed high specificity (86%) and sensitivity across all CRC stages (95%) and adenomatous lesions (79%). The area under the curve was 0.940 and 0.868 for the detection of CRC and adenomas, respectively. DISCUSSION The blood-based CTC platform demonstrated high sensitivity in detecting adenomas and CRC, as well as reasonable specificity in an enriched symptomatic patient population. TRANSLATIONAL IMPACT If these results are reproduced in an average risk population, this test has the potential to prevent CRC by improving patient compliance and detecting precancerous adenomas, eventually reducing CRC mortality.
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Ahrens TD, Bang-Christensen SR, Jørgensen AM, Løppke C, Spliid CB, Sand NT, Clausen TM, Salanti A, Agerbæk MØ. The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis. Front Cell Dev Biol 2020; 8:749. [PMID: 32984308 PMCID: PMC7479181 DOI: 10.3389/fcell.2020.00749] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/17/2020] [Indexed: 12/14/2022] Open
Abstract
Circulating tumor cells (CTCs) are accessible by liquid biopsies via an easy blood draw. They represent not only the primary tumor site, but also potential metastatic lesions, and could thus be an attractive supplement for cancer diagnostics. However, the analysis of rare CTCs in billions of normal blood cells is still technically challenging and novel specific CTC markers are needed. The formation of metastasis is a complex process supported by numerous molecular alterations, and thus novel CTC markers might be found by focusing on this process. One example of this is specific changes in the cancer cell glycocalyx, which is a network on the cell surface composed of carbohydrate structures. Proteoglycans are important glycocalyx components and consist of a protein core and covalently attached long glycosaminoglycan chains. A few CTC assays have already utilized proteoglycans for both enrichment and analysis of CTCs. Nonetheless, the biological function of proteoglycans on clinical CTCs has not been studied in detail so far. Therefore, the present review describes proteoglycan functions during the metastatic cascade to highlight their importance to CTCs. We also outline current approaches for CTC assays based on targeting proteoglycans by their protein cores or their glycosaminoglycan chains. Lastly, we briefly discuss important technical aspects, which should be considered for studying proteoglycans.
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Affiliation(s)
- Theresa D. Ahrens
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
| | - Sara R. Bang-Christensen
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
- VarCT Diagnostics, Copenhagen, Denmark
| | | | - Caroline Løppke
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
| | - Charlotte B. Spliid
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States
| | - Nicolai T. Sand
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
| | - Thomas M. Clausen
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, United States
| | - Ali Salanti
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
| | - Mette Ø. Agerbæk
- Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
- VarCT Diagnostics, Copenhagen, Denmark
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Lee LX, Li SC. Hunting down the dominating subclone of cancer stem cells as a potential new therapeutic target in multiple myeloma: An artificial intelligence perspective. World J Stem Cells 2020; 12:706-720. [PMID: 32952853 PMCID: PMC7477658 DOI: 10.4252/wjsc.v12.i8.706] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/08/2020] [Accepted: 08/14/2020] [Indexed: 02/07/2023] Open
Abstract
The development of single-cell subclones, which can rapidly switch from dormant to dominant subclones, occur in the natural pathophysiology of multiple myeloma (MM) but is often "pressed" by the standard treatment of MM. These emerging subclones present a challenge, providing reservoirs for chemoresistant mutations. Technological advancement is required to track MM subclonal changes, as understanding MM's mechanism of evolution at the cellular level can prompt the development of new targeted ways of treating this disease. Current methods to study the evolution of subclones in MM rely on technologies capable of phenotypically and genotypically characterizing plasma cells, which include immunohistochemistry, flow cytometry, or cytogenetics. Still, all of these technologies may be limited by the sensitivity for picking up rare events. In contrast, more incisive methods such as RNA sequencing, comparative genomic hybridization, or whole-genome sequencing are not yet commonly used in clinical practice. Here we introduce the epidemiological diagnosis and prognosis of MM and review current methods for evaluating MM subclone evolution, such as minimal residual disease/multiparametric flow cytometry/next-generation sequencing, and their respective advantages and disadvantages. In addition, we propose our new single-cell method of evaluation to understand MM's mechanism of evolution at the molecular and cellular level and to prompt the development of new targeted ways of treating this disease, which has a broad prospect.
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Affiliation(s)
- Lisa X Lee
- Division of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, UCI Health, Orange, CA 92868, United States
| | - Shengwen Calvin Li
- Neuro-oncology and Stem Cell Research Laboratory, CHOC Children's Research Institute, Children's Hospital of Orange County, Orange, CA 92868, United States
- Department of Neurology, University of California-Irvine School of Medicine, Orange, CA 92868, United States.
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Circulating Tumour DNAs and Non-Coding RNAs as Liquid Biopsies for the Management of Colorectal Cancer Patients. GASTROINTESTINAL DISORDERS 2020. [DOI: 10.3390/gidisord2030022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Circulating tumour DNAs and non-coding RNAs present in body fluids have been under investigation as tools for cancer diagnosis, disease monitoring, and prognosis for many years. These so-called liquid biopsies offer the opportunity to obtain information about the molecular make-up of a cancer in a minimal invasive way and offer the possibility to implement theranostics for precision oncology. Furthermore, liquid biopsies could overcome the limitations of tissue biopsies in capturing the complexity of tumour heterogeneity within the primary cancer and among different metastatic sites. Liquid biopsies may also be implemented to detect early tumour formation or to monitor cancer relapse of response to therapy with greater sensitivity compared with the currently available protein-based blood biomarkers. Most colorectal cancers are often diagnosed at late stages and have a high mortality rate. Hence, biomolecules as nucleic acids present in liquid biopsies might have prognostic potential and could serve as predictive biomarkers for chemotherapeutic regimens. This review will focus on the role of circulating tumour DNAs and non-coding RNAs as diagnostic, prognostic, and predictive biomarkers in the context of colorectal cancer.
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Akpe V, Kim TH, Brown CL, Cock IE. Circulating tumour cells: a broad perspective. J R Soc Interface 2020; 17:20200065. [PMCID: PMC7423436 DOI: 10.1098/rsif.2020.0065] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 07/09/2020] [Indexed: 08/13/2023] Open
Abstract
Circulating tumour cells (CTCs) have recently been identified as valuable biomarkers for diagnostic and prognostic evaluations, as well for monitoring therapeutic responses to treatments. CTCs are rare cells which may be present as one CTC surrounded by approximately 1 million white blood cells and 1 billion red blood cells per millilitre of peripheral blood. Despite the various challenges in CTC detection, considerable progress in detection methods have been documented in recent times, particularly for methodologies incorporating nanomaterial-based platforms and/or integrated microfluidics. Herein, we summarize the importance of CTCs as biological markers for tumour detection, highlight their mechanism of cellular invasion and discuss the various challenges associated with CTC research, including vulnerability, heterogeneity, phenotypicity and size differences. In addition, we describe nanomaterial agents used for electrochemistry and surface plasmon resonance applications, which have recently been used to selectively capture cancer cells and amplify signals for CTC detection. The intrinsic properties of nanomaterials have also recently been exploited to achieve photothermal destruction of cancer cells. This review describes recent advancements and future perspectives in the CTC field.
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Affiliation(s)
- Victor Akpe
- School of Environment and Science, Griffith University, Nathan Campus, Queensland 4111, Australia
- Environmental Futures Research Institute, Griffith University, Nathan Campus, Queensland 4111, Australia
| | - Tak H. Kim
- School of Environment and Science, Griffith University, Nathan Campus, Queensland 4111, Australia
- Environmental Futures Research Institute, Griffith University, Nathan Campus, Queensland 4111, Australia
| | - Christopher L. Brown
- School of Environment and Science, Griffith University, Nathan Campus, Queensland 4111, Australia
- Environmental Futures Research Institute, Griffith University, Nathan Campus, Queensland 4111, Australia
| | - Ian E. Cock
- School of Environment and Science, Griffith University, Nathan Campus, Queensland 4111, Australia
- Environmental Futures Research Institute, Griffith University, Nathan Campus, Queensland 4111, Australia
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Poggiana C, Rossi E, Zamarchi R. Possible role of circulating tumor cells in early detection of lung cancer. J Thorac Dis 2020; 12:3821-3835. [PMID: 32802464 PMCID: PMC7399415 DOI: 10.21037/jtd.2020.02.24] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The prognosis of lung cancer varies highly depending on the disease stage at diagnosis, from a 5-year survival rate close to 90% in stage I, to 10% or less in stage IV disease. The enhancement of early diagnosis of this malignancy is mandatory to improve prognosis, because lung cancer patients stay long asymptomatic or few symptomatic after disease onset. Nowadays, liquid biopsy has emerged as a minimally-invasive tool to address the urgent need for real time monitoring, stratification, and personalized treatment of malignancies, including lung cancer. Liquid biopsy refers to a class of biomarkers, including circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA) and tumor-derived extracellular vesicles (tdEV). Since CTCs represent a crucial step in disease progression and metastasis, we reviewed here the scientific literature about the use of CTCs in early diagnosis of lung cancer; different techniques, and different strategies (e.g., source of analysis sample or high-risk groups of patients) were discussed showing the potential of implementing liquid biopsy in the clinical routine of non-metastatic lung cancer.
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Affiliation(s)
| | - Elisabetta Rossi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.,Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Rita Zamarchi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
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47
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Narayan P, Ghosh S, Philip R, Barrett JC, McCormack RT, Odegaard JI, R Oxnard G, Pracht LJ, Williams PM, Kelloff GJ, Beaver JA. State of the Science and Future Directions for Liquid Biopsies in Drug Development. Oncologist 2020; 25:730-732. [PMID: 32510742 DOI: 10.1634/theoncologist.2020-0246] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 05/01/2020] [Indexed: 11/17/2022] Open
Affiliation(s)
- Preeti Narayan
- Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Soma Ghosh
- Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Reena Philip
- Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - J Carl Barrett
- AstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA
| | | | | | - Geoffrey R Oxnard
- Dana-Farber Cancer Institute, Harvard University, Boston, Massachusetts, USA
| | - Laurel J Pracht
- Patient Advocate, National Cancer Institute, Bethesda, Maryland, USA
| | - P Mickey Williams
- Frederick National Laboratories for Cancer Research, Frederick, Maryland, USA
| | | | - Julia A Beaver
- Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
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Abstract
Background
The effect of anesthetic drugs on cancer outcomes remains unclear. This trial aimed to assess postoperative circulating tumor cell counts—an independent prognostic factor for breast cancer—to determine how anesthesia may indirectly affect prognosis. It was hypothesized that patients receiving sevoflurane would have higher postoperative tumor cell counts.
Methods
The parallel, randomized controlled trial was conducted in two centers in Switzerland. Patients aged 18 to 85 yr without metastases and scheduled for primary breast cancer surgery were eligible. The patients were randomly assigned to either sevoflurane or propofol anesthesia. The patients and outcome assessors were blinded. The primary outcome was circulating tumor cell counts over time, assessed at three time points postoperatively (0, 48, and 72 h) by the CellSearch assay. Secondary outcomes included maximal circulating tumor cells value, positivity (cutoff: at least 1 and at least 5 tumor cells/7.5 ml blood), and the association between natural killer cell activity and tumor cell counts. This trial was registered with ClinicalTrials.gov (NCT02005770).
Results
Between March 2014 and April 2018, 210 participants were enrolled, assigned to sevoflurane (n = 107) or propofol (n = 103) anesthesia, and eventually included in the analysis. Anesthesia type did not affect circulating tumor cell counts over time (median circulating tumor cell count [interquartile range]; for propofol: 1 [0 to 4] at 0 h, 1 [0 to 2] at 48 h, and 0 [0 to 1] at 72 h; and for sevoflurane: 1 [0 to 4] at 0 h, 0 [0 to 2] at 48 h, and 1 [0 to 2] at 72 h; rate ratio, 1.27 [95% CI, 0.95 to 1.71]; P = 0.103) or positivity. In one secondary analysis, administrating sevoflurane led to a significant increase in maximal tumor cell counts postoperatively. There was no association between natural killer cell activity and circulating tumor cell counts.
Conclusions
In this randomized controlled trial investigating the effect of anesthesia on an independent prognostic factor for breast cancer, there was no difference between sevoflurane and propofol with respect to circulating tumor cell counts over time.
Editor’s Perspective
What We Already Know about This Topic
What This Article Tells Us That Is New
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Song Y, Jia Z, Wang Y, Wang Y, Liu P, Zhang S, Bing Z, Cao L, Cao Z, Rossi E, Zamarchi R, Denis MG, Camps C, Fernandez-Diaz AB, Liang N, Li S. Potential treatment strategy for the rare osimertinib resistant mutation EGFR L718Q. J Thorac Dis 2020; 12:2771-2780. [PMID: 32642185 PMCID: PMC7330377 DOI: 10.21037/jtd.2020.03.29] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 02/25/2020] [Indexed: 01/07/2023]
Abstract
Epidermal growth factor receptor (EGFR) L718Q is a rare resistant mutation which independently leads to third-generation tyrosine kinase inhibitor (TKI) resistance. Although a few studies have examined its resistance mechanisms, no effective treatment strategy has yet been proposed for patients with this mutation. Here, we report an effective treatment strategy for the rare EGFR L718Q mutation for the first time. A 44-year-old Chinese male patient initially presented with the sensitizing EGFR L858R mutation, and the progression-free survival (PFS) time after initial icotinib treatment was 9 months. When the progression of the disease (PD) and the EGFR T790M mutation were identified, he did not respond to the osimertinib treatment. Through comprehensive next-generation sequencing (NGS) of the surgical specimen, the rare EGFR L718Q mutation was eventually identified as having a frequency of 68.84%, together with an EGFR amplification with a copy number of 11.54. The previous treatment response was retrospectively explained, and the patient faced the challenge of not being able to benefit from any targeted therapy. Following chemotherapy with a personalized regimen which effectively modified the proportion of sensitive and resistant cells, significant response to osimertinib re-challenge was observed, and another PFS of 4.7 months was achieved. Unfortunately, four EGFR mutations, EGFR L858, T790M, L718Q, and C797S, were simultaneously detected in his late stage, and led to further progression of disease.
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Affiliation(s)
- Yang Song
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Ziqi Jia
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
- Peking Union Medical College, Eight-Year MD Program, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yadong Wang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yanyu Wang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Peng Liu
- Medical Research Center, Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Shuyang Zhang
- Medical Research Center, Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Zhongxing Bing
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Lei Cao
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Zhili Cao
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Elisabetta Rossi
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Rita Zamarchi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Marc G. Denis
- Department of Biochemistry and INSERM U1232, Nantes University Hospital, 9 quai Moncousu, F-44093 Nantes Cedex, France
| | - Carlos Camps
- Molecular Oncology Laboratory, General University Hospital Research Foundation, ValenciaSpain
- CIBERONC, Madrid, Spain
- Unidad Mixta TRIAL CIPF-FIHGUV, Valencia, Spain
- Medical Oncology Department, Hospital General Universitario de Valencia, Medicine Department, Universidad de Valencia, Spain
| | - Amaya B. Fernandez-Diaz
- Medical Oncology Department, Hospital General Universitario de Valencia, Medicine Department, Universidad de Valencia, Spain
| | - Naixin Liang
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Shanqing Li
- Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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Bao-Caamano A, Rodriguez-Casanova A, Diaz-Lagares A. Epigenetics of Circulating Tumor Cells in Breast Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1220:117-134. [PMID: 32304083 DOI: 10.1007/978-3-030-35805-1_8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liquid biopsy based on the analysis of circulating tumor cells (CTCs) has emerged as an important field of research. Molecular characterization of CTCs can provide insights into cancer biology and biomarkers for the clinic, representing a non-invasive powerful tool for monitoring breast cancer metastasis and predict the therapeutic response. Epigenetic mechanisms play a key role in the control of gene expression and their alteration contributes to cancer development and progression. These epigenetic modifications in CTCs have been described mainly related to modifications of the DNA methylation pattern and changes in the expression profile of noncoding RNAs. Here we summarize the recent findings on the epigenetic characterization of CTCs in breast cancer and their clinical value as tumor biomarkers, and discuss challenges and opportunities in this field.
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Affiliation(s)
- Aida Bao-Caamano
- Cancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain
| | - Aitor Rodriguez-Casanova
- Cancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.,Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain
| | - Angel Diaz-Lagares
- Cancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. .,Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
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