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Lewis F, Ward MP, Saadeh FA, O'Gorman C, Maguire PJ, Beirne JP, Kamran W, Ibrahim E, Norris L, Kelly T, Hurley S, Henderson B, Kanjuga M, O'Driscoll L, Gately K, Oner E, Saini VM, Cadoo K, Martin C, O'Leary JJ, O'Toole SA. A pilot study evaluating the feasibility of enriching and detecting circulating tumour cells from peripheral and ovarian veins in rare epithelial ovarian carcinomas. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109721. [PMID: 40348476 DOI: 10.1016/j.ejso.2025.109721] [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: 12/23/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 05/14/2025]
Abstract
INTRODUCTION Studies on circulating tumour cells (CTCs) in rare epithelial ovarian carcinomas (EOC) are limited, despite their potential as a minimally invasive biomarker for monitoring cancer progression and predicting outcomes. This pilot study aimed to assess the feasibility of enriching and detecting CTCs from both peripheral and ovarian vein blood samples in rare EOC subtypes. MATERIALS AND METHODS Blood samples were collected from the peripheral and ovarian veins of 20 patients with rare EOC. Among the 20 patients, 12 had early-stage disease (I-II), while 8 had advanced disease (III-IV). CTCs were enriched using the Parsortix® system and immunophenotyped via immunofluorescence targeting epithelial markers (EpCAM/pan-cytokeratin) and Hoechst for positive selection, and CD45 for negative selection. CTC status (positive versus negative) was correlated with clinicopathological data. RESULTS CTCs were successfully detected in 45 % (1-19 CTCs) of baseline peripheral samples and 55 % (1-4776 CTCs) of ovarian vein samples. CTC doublets and clusters were detected in ovarian vein samples (3/11), but not in peripheral samples (0/20). A higher proportion of deaths were observed in CTC+ patients compared to CTC- patients (p = 0.0088). CONCLUSION Here we demonstrate the feasibility of enriching and detecting CTCs from both peripheral and ovarian vein blood in patients with rare EOC. The higher CTC yield in ovarian vein blood suggests that tumour-draining blood may play a role in improving CTC detection. This pilot study paves the way for larger studies to investigate the prognostic utility of CTCs and refine their clinical value in these rare understudied EOC.
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Affiliation(s)
- Faye Lewis
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
| | - Mark P Ward
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Feras Abu Saadeh
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Catherine O'Gorman
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Patrick J Maguire
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - James P Beirne
- Blackrock Health Hermitage Clinic, Old Lucan Road, Dublin, Ireland
| | - Waseem Kamran
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Elzahra Ibrahim
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Lucy Norris
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Tanya Kelly
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Sinéad Hurley
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Brian Henderson
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Marika Kanjuga
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Lorraine O'Driscoll
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland; Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland
| | - Kathy Gately
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Ezgi Oner
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Volga M Saini
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Karen Cadoo
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; The Haematology, Oncology and Palliative Care (HOPe) Directorate, St James's Hospital, Dublin, Ireland
| | - Cara Martin
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - John J O'Leary
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Sharon A O'Toole
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
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Pérez-Cabello JA, Artero-Castro A, Molina-Pinelo S. Small cell lung cancer unveiled: Exploring the untapped resource of circulating tumor cells-derived organoids. Crit Rev Oncol Hematol 2025; 207:104622. [PMID: 39832682 DOI: 10.1016/j.critrevonc.2025.104622] [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: 10/01/2024] [Revised: 01/09/2025] [Accepted: 01/14/2025] [Indexed: 01/22/2025] Open
Abstract
Small cell lung cancer (SCLC) remains a challenge in oncology due to its aggressive behavior and dismal prognosis. Despite advances in treatments, novel strategies are urgently needed. Enter liquid biopsy-a game-changer in SCLC management. This revolutionary non-invasive approach allows for the analysis of circulating tumor cells (CTCs), offering insights into tumor behavior and treatment responses. Our review focuses on a groundbreaking frontier: harnessing CTCs to create three-dimensional (3D) organoid models. These models, derived from CTCs that break away from the primary tumor or metastatic locations, hold immense potential for revolutionizing cancer research, especially in SCLC. We explore the essential conditions for successfully establishing CTC-derived organoids-a transformative approach with profound implications for personalized medicine. Our evaluation spans diverse isolation techniques, shedding light on their advantages and limitations. Furthermore, we uncover the critical factors governing the cultivation of 3D organoids from CTCs, meticulously mimicking the tumor microenvironment. This review comprehensively elucidates the molecular characterization of these organoids, showcasing their potential in identifying treatment targets and predicting responses. In essence, our review amalgamates cutting-edge methodologies for isolating CTCs, establishing transformative CTC-derived organoids, and characterizing their molecular landscape. This represents a promising frontier for advancing personalized medicine in the complex realm of SCLC management and holds significant implications for translational research.
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Affiliation(s)
- Jesús A Pérez-Cabello
- Institute of Biomedicine of Seville (IBiS), HUVR, CSIC, University of Seville, Seville 41013, Spain
| | - Ana Artero-Castro
- Institute of Biomedicine of Seville (IBiS), HUVR, CSIC, University of Seville, Seville 41013, Spain
| | - Sonia Molina-Pinelo
- Institute of Biomedicine of Seville (IBiS), HUVR, CSIC, University of Seville, Seville 41013, Spain; Spanish Center for Biomedical Research Network in Oncology (CIBERONC), Madrid 28029, Spain.
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Park J, Lee YT, Agopian VG, Liu JS, Koltsova EK, You S, Zhu Y, Tseng HR, Yang JD. Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications. Clin Mol Hepatol 2025; 31:S255-S284. [PMID: 39604328 PMCID: PMC11925447 DOI: 10.3350/cmh.2024.0541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/15/2024] [Accepted: 11/25/2024] [Indexed: 11/29/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional's skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.
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Affiliation(s)
- Jaeho Park
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Yi-Te Lee
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Vatche G. Agopian
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
| | - Jessica S Liu
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
| | - Ekaterina K. Koltsova
- Smidt Heart Institute, Department of Medicine, Department of Biomedical Sciences, 8700 Beverly Blvd, Los Angeles, CA, USA
| | - Sungyong You
- Department of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Yazhen Zhu
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA
| | - Hsian-Rong Tseng
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Yun Y, Kim S, Lee SN, Cho HY, Choi JW. Nanomaterial-based detection of circulating tumor cells and circulating cancer stem cells for cancer immunotherapy. NANO CONVERGENCE 2024; 11:56. [PMID: 39671082 PMCID: PMC11645384 DOI: 10.1186/s40580-024-00466-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 12/04/2024] [Indexed: 12/14/2024]
Abstract
Nanomaterials have emerged as transformative tools for detecting circulating tumor cells (CTCs) and circulating cancer stem cells (CCSCs), significantly enhancing cancer diagnostics and immunotherapy. Nanomaterials, including those composed of gold, magnetic materials, and silica, have enhanced the sensitivity, specificity, and efficiency of isolating these rare cells from blood. These developments are of paramount importance for the early detection of cancer and for providing real-time insights into metastasis and treatment resistance, which are essential for the development of personalized immunotherapies. The combination of nanomaterial-based platforms with phenotyping techniques, such as Raman spectroscopy and microfluidics, enables researchers to enhance immunotherapy protocols targeting specific CTC and CCSC markers. Nanomaterials also facilitate the targeted delivery of immunotherapeutic agents, including immune checkpoint inhibitors and therapeutic antibodies, directly to tumor cells. This synergistic approach has the potential to enhance therapeutic efficacy and mitigate the risk of metastasis and relapse. In conclusion, this review critically examines the use of nanomaterial-driven detection systems for detecting CTCs and CCSCs, their application in immunotherapy, and suggests future directions, highlighting their potential to transform the integration of diagnostics and treatment, thereby paving the way for more precise and personalized cancer therapies.
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Affiliation(s)
- Yeochan Yun
- Department of Bio and Fermentation Convergence Technology, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul, 02707, Republic of Korea
| | - Seewoo Kim
- Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 04107, Republic of Korea
| | - Sang-Nam Lee
- Uniance Gene Inc., 273, Digital-ro, Guro-gu, Seoul, 08381, Republic of Korea.
| | - Hyeon-Yeol Cho
- Department of Bio and Fermentation Convergence Technology, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul, 02707, Republic of Korea.
| | - Jeong-Woo Choi
- Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 04107, Republic of Korea.
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Lewis F, Beirne J, Henderson B, Norris L, Cadoo K, Kelly T, Martin C, Hurley S, Kanjuga M, O'Driscoll L, Gately K, Oner E, Saini VM, Brooks D, Selemidis S, Kamran W, Haughey N, Maguire P, O'Gorman C, Saadeh FA, Ward MP, O'Leary JJ, O'Toole SA. Unravelling the biological and clinical challenges of circulating tumour cells in epithelial ovarian carcinoma. Cancer Lett 2024; 605:217279. [PMID: 39341451 DOI: 10.1016/j.canlet.2024.217279] [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: 07/04/2024] [Revised: 09/22/2024] [Accepted: 09/24/2024] [Indexed: 10/01/2024]
Abstract
Epithelial ovarian carcinoma (EOC) is the eighth most common cancer in women and the leading cause of gynaecological cancer death, predominantly due to the absence of effective screening tools, advanced stage at diagnosis, and high rates of recurrence. Circulating tumour cells (CTCs), a rare subset of tumour cells that disseminate from a tumour and migrate into the circulation, play a pivotal role in the metastatic cascade, and therefore hold promise as biomarkers for disease monitoring and prognostication. Exploring CTCs from liquid biopsies is an appealing approach for research and clinical practice, given it is minimally invasive, facilitates serial sampling and enables the capture of the entire spectrum of cancer cells circulating in the blood. The prognostic utility of CTC enumeration has been FDA-approved for clinical use in metastatic breast, prostate, and colorectal cancers. However, the unique biology of EOC, discussed herein, compounds the detection and characterisation complexities already inherent in CTC research, consequently hindering progress towards clinical applications. The aim of this review is to provide an overview of both the biological and clinical challenges encountered in harnessing the power of CTCs in EOC.
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Affiliation(s)
- Faye Lewis
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - James Beirne
- Blackrock Health Hermitage Clinic, Old Lucan Road, Dublin, Ireland
| | - Brian Henderson
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Lucy Norris
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Karen Cadoo
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; The Haematology, Oncology and Palliative Care (HOPe) Directorate, St James's Hospital, Dublin, Ireland
| | - Tanya Kelly
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Cara Martin
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Sinéad Hurley
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Marika Kanjuga
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland
| | - Lorraine O'Driscoll
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland; Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland
| | - Kathy Gately
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Ezgi Oner
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Volga M Saini
- Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Ireland; Thoracic Oncology Research Group, Trinity Translational Medicine Institute, St James's Hospital, Dublin, Ireland
| | - Doug Brooks
- Cancer Research Institute, University of South Australia, 5001, Adelaide, Australia
| | - Stavros Selemidis
- School of Health and Biomedical Sciences, RMIT University, Victoria, 3083, Bundoora, Australia
| | - Waseem Kamran
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Niamh Haughey
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Patrick Maguire
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Catherine O'Gorman
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Feras Abu Saadeh
- Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland; Division of Gynaecological Oncology, St James's Hospital, Dublin, Ireland
| | - Mark P Ward
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
| | - John J O'Leary
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
| | - Sharon A O'Toole
- Department of Histopathology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Department of Obstetrics and Gynaecology, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
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Ke H, Kao S, van Zandwijk N, Rasko JEJ, Yeo D. Circulating tumor cell detection may offer earlier diagnosis in patients suspected of asbestos-related lung cancer. Lung Cancer 2024; 192:107829. [PMID: 38810528 DOI: 10.1016/j.lungcan.2024.107829] [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: 02/13/2024] [Accepted: 05/21/2024] [Indexed: 05/31/2024]
Abstract
Asbestos-Related Lung Cancer (ARLC) presents ongoing diagnostic challenges despite improved imaging technologies. The long latency period, coupled with limited access to occupational and environmental data along with the confounding effects of smoking and other carcinogens adds complexity to the diagnostic process. Compounding these challenges is the absence of a specific histopathologic or mutational signature of ARLC. A correlation between PD-L1 expression and response to immune checkpoint inhibition has not yet been proven. Thus, new biomarkers are needed to allow accurate diagnoses of ARLC, to enable prognostication and to offer personalized treatments. Liquid biopsies, encompassing circulating DNA and circulating tumor cells (CTCs), have gained attention as novel diagnostic methods in lung cancer to screen high-risk populations including those exposed to asbestos. CTCs can be enumerated and molecularly profiled to provide predictive and prognostic information. CTC studies have not been undertaken in populations at risk of ARLC to date. The potential of CTCs to provide real-time molecular insight into ARLC biology may significantly improve the diagnosis and management of ARLC patients.
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Affiliation(s)
- Helen Ke
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, 2050 NSW, Australia; Precision Oncology Laboratory, Gene and Stem Cell Therapy Program, Centenary Institute, The University of Sydney, Camperdown, 2050 NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, 2050 NSW, Australia; Medical Oncology, Chris O'Brien Lifehouse, NSW 2050 Camperdown, Australia
| | - Steven Kao
- Faculty of Medicine and Health, The University of Sydney, Camperdown, 2050 NSW, Australia; Medical Oncology, Chris O'Brien Lifehouse, NSW 2050 Camperdown, Australia; Asbestos Diseases Research Institute, NSW 2139 Concord, Australia
| | - Nico van Zandwijk
- Faculty of Medicine and Health, The University of Sydney, Camperdown, 2050 NSW, Australia; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District (SLHD), Camperdown, 2050 NSW, Australia
| | - John E J Rasko
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, 2050 NSW, Australia; Precision Oncology Laboratory, Gene and Stem Cell Therapy Program, Centenary Institute, The University of Sydney, Camperdown, 2050 NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, 2050 NSW, Australia; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District (SLHD), Camperdown, 2050 NSW, Australia.
| | - Dannel Yeo
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, 2050 NSW, Australia; Precision Oncology Laboratory, Gene and Stem Cell Therapy Program, Centenary Institute, The University of Sydney, Camperdown, 2050 NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, 2050 NSW, Australia; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District (SLHD), Camperdown, 2050 NSW, Australia.
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Murray NP. Biomarkers of minimal residual disease and treatment. Adv Clin Chem 2024; 119:33-70. [PMID: 38514211 DOI: 10.1016/bs.acc.2024.02.002] [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] [Indexed: 03/23/2024]
Abstract
Minimal residual disease (MRD) has been defined as a very small numbers of cancer cells that remain in the body after curative treatment. Its presence or absence will ultimately determine prognosis. With the introduction of new technologies the presence of MRD in patients with solid tumours can be detected and characterized. As MRD predicts future relapse, be it early or late treatment failure, in an otherwise asymptomatic patient its treatment and when to start treatment remains to be determined. Thus the concepts of personalized medicine using different biomarkers to classify the biological properties of MRD maybe come possible. Based on this determinations it may be possible to use targeted therapies rather than all patients with the same type of cancer receiving a standard treatment. However, it is important to understand the limitations of the different technologies, what these techniques are detecting and how they may help in the treatment of patients with cancer. The majority of published studies are in patients with metastatic cancer and there are few reports in patients with MRD. In this chapter the concept of MRD, the methods used to detect it and what treatments may be effective based on the biological characteristics of the tumour cells as determined by different biomarkers is reviewed. MRD depends on the phenotypic properties of the tumour cells to survive in their new environment and the anti-tumour immune response. This is a dynamic process and changes with time in the wake of immunosuppression caused by the tumour cells and/or the effects of treatment to select resistant tumour cells. With the use of biomarkers to typify the characteristics of MRD and the development of new drugs a personalized treatment can be designed rather than all patients given the same treatment. Patients who are initially negative for MRD may not require further treatment with liquid biopsies used to monitor the patients during follow-up in order to detect those patients who may become MRD positive. The liquid biopsy used during the follow up of MRD positive patients can be used to detect changes in the biological properties of the tumour cells and thus may need treatment changes to overcome tumour cell resistance.
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Affiliation(s)
- Nigel P Murray
- Minimal Residual Disease Laboratory, Faculty of Medicine, University Finis Terrae, Santiago, Chile.
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Kahounová Z, Pícková M, Drápela S, Bouchal J, Szczyrbová E, Navrátil J, Souček K. Circulating tumor cell-derived preclinical models: current status and future perspectives. Cell Death Dis 2023; 14:530. [PMID: 37591867 PMCID: PMC10435501 DOI: 10.1038/s41419-023-06059-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 08/01/2023] [Accepted: 08/10/2023] [Indexed: 08/19/2023]
Abstract
Despite the advancements made in the diagnosis and treatment of cancer, the stages associated with metastasis remain largely incurable and represent the primary cause of cancer-related deaths. The dissemination of cancer is facilitated by circulating tumor cells (CTCs), which originate from the primary tumor or metastatic sites and enter the bloodstream, subsequently spreading to distant parts of the body. CTCs have garnered significant attention in research due to their accessibility in peripheral blood, despite their low abundance. They are being extensively studied to gain a deeper understanding of the mechanisms underlying cancer dissemination and to identify effective therapeutic strategies for advanced stages of the disease. Therefore, substantial efforts have been directed towards establishing and characterizing relevant experimental models derived from CTCs, aiming to provide relevant tools for research. In this review, we provide an overview of recent progress in the establishment of preclinical CTC-derived models, such as CTC-derived xenografts (CDX) and cell cultures, which show promise for the study of CTCs. We discuss the advantages and limitations of these models and conclude by summarizing the potential future use of CTCs and CTC-derived models in cancer treatment decisions and their utility as precision medicine tools.
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Affiliation(s)
- Zuzana Kahounová
- Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 612 00, Brno, Czech Republic
| | - Markéta Pícková
- Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 612 00, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital, 602 00, Brno, Czech Republic
- Department of Experimental Biology, Faculty of Science, Masaryk University, 625 00, Brno, Czech Republic
| | - Stanislav Drápela
- Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 612 00, Brno, Czech Republic
- International Clinical Research Center, St. Anne's University Hospital, 602 00, Brno, Czech Republic
- Department of Experimental Biology, Faculty of Science, Masaryk University, 625 00, Brno, Czech Republic
- Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Jan Bouchal
- Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital, 779 00, Olomouc, Czech Republic
| | - Eva Szczyrbová
- Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital, 779 00, Olomouc, Czech Republic
| | - Jiří Navrátil
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53, Brno, Czech Republic
| | - Karel Souček
- Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, 612 00, Brno, Czech Republic.
- International Clinical Research Center, St. Anne's University Hospital, 602 00, Brno, Czech Republic.
- Department of Experimental Biology, Faculty of Science, Masaryk University, 625 00, Brno, Czech Republic.
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9
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Halawa T, Baeesa S, Fadul MM, Badahdah AA, Enani M, Fathaddin AA, Kawass D, Alkhotani A, Bahakeem B, Kurdi M. The Role of Liquid Biopsy in the Diagnosis and Prognosis of WHO Grade 4 Astrocytoma. Cureus 2023; 15:e41221. [PMID: 37525780 PMCID: PMC10387356 DOI: 10.7759/cureus.41221] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2023] [Indexed: 08/02/2023] Open
Abstract
Liquid biopsy, as a non-invasive diagnostic tool, has recently gained significant attention in the field of oncology. It involves the analysis of various biomarkers present in bodily fluids, such as blood or cerebrospinal fluid, to provide information about the underlying cancer. In the case of WHO grade 4 astrocytomas, liquid biopsy has the potential to significantly impact the diagnosis and prognosis of this aggressive malignant brain tumor. By detecting specific genetic mutations, such as IDH1 or EGFR, and monitoring levels of circulating tumor DNA, liquid biopsy can aid in the early detection and monitoring of disease progression. This innovative approach is gradually being acknowledged as a less invasive and cost-effective procedure for cancer diagnosis and management to improve patient outcomes and quality of life. Various kinds of biomarkers circulating in cerebrospinal fluid (CSF), such as circulating tumor cells (CTC) and different types of nucleic acids like cell-free DNA (cfDNA), cell-free RNA (ctRNA), and microRNAs (miRNA), have been identified. These biomarkers, which require dependable detection methods, are comparatively simple to obtain and allow for repeated measurements, making them significantly superior for disease monitoring. This review aims to compare the latest liquid biopsy analysis tools for both CSF and plasma in the central nervous system.
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Affiliation(s)
- Taher Halawa
- Department of Pediatrics, Faculty of Medicine King Abdulaziz University, Rabigh, SAU
| | - Saleh Baeesa
- Department of Neuroscience, King Faisal Specialist Hospital and Research Centre, Jeddah, SAU
| | - Motaz M Fadul
- Department of Pathology, Faculty of Medicine King Abdulaziz University, Rabigh, SAU
| | - Adnan A Badahdah
- Department of Internal Medicine, University of Jeddah, Jeddah, SAU
| | - Maryam Enani
- Department of Surgery, King Abdulaziz University Hospital, Jeddah, SAU
| | - Amany A Fathaddin
- Department of Pathology, College of Medicine, King Saud University, Riyadh, SAU
- Department of Pathology, King Saud University Medical City, Riyadh, SAU
| | - Dania Kawass
- Department of Family Medicine, Faculty of Medicine King Abdulaziz University, Jeddah, SAU
| | - Alaa Alkhotani
- Department of Pathology, Umm Al-Qura University, Makkah, SAU
| | - Basem Bahakeem
- Department of Internal Medicine, Umm Al-Qura University, Makkah, SAU
| | - Maher Kurdi
- Department of Pathology, Faculty of Medicine King Abdulaziz University, Rabigh, SAU
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10
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Ancel J, Dormoy V, Raby BN, Dalstein V, Durlach A, Dewolf M, Gilles C, Polette M, Deslée G. Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors. Front Immunol 2023; 14:1171649. [PMID: 37283751 PMCID: PMC10239865 DOI: 10.3389/fimmu.2023.1171649] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 05/11/2023] [Indexed: 06/08/2023] Open
Abstract
Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological-driven decision.
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Affiliation(s)
- Julien Ancel
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
- Department of Respiratory Diseases, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, Reims, France
| | - Valérian Dormoy
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
| | - Béatrice Nawrocki Raby
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
| | - Véronique Dalstein
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
- Department of Biopathology, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, Reims, France
| | - Anne Durlach
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
- Department of Biopathology, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, Reims, France
| | - Maxime Dewolf
- Department of Respiratory Diseases, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, Reims, France
| | - Christine Gilles
- Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium
| | - Myriam Polette
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
- Department of Biopathology, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, Reims, France
| | - Gaëtan Deslée
- Inserm UMR-S1250, P3Cell, University of Reims Champagne-Ardenne, SFR CAP-SANTE, Reims, France
- Department of Respiratory Diseases, Centre Hospitalier Universitaire de Reims, Hôpital Maison Blanche, Reims, France
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11
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Asawa S, Nüesch M, Gvozdenovic A, Aceto N. Circulating tumour cells in gastrointestinal cancers: food for thought? Br J Cancer 2023; 128:1981-1990. [PMID: 36932192 DOI: 10.1038/s41416-023-02228-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/17/2023] [Accepted: 03/02/2023] [Indexed: 03/19/2023] Open
Abstract
Gastrointestinal (GI) cancers account for 35% of cancer-related deaths, predominantly due to their ability to spread and generate drug-tolerant metastases. Arising from different locations in the GI system, the majority of metastatic GI malignancies colonise the liver and the lungs. In this context, circulating tumour cells (CTCs) are playing a critical role in the formation of new metastases, and their presence in the blood of patients has been correlated with a poor outcome. In addition to their prognostic utility, prospective targeting of CTCs may represent a novel, yet ambitious strategy in the fight against metastasis. A better understanding of CTC biology, mechanistic underpinnings and weaknesses may facilitate the development of previously underappreciated anti-metastasis approaches. Here, along with related clinical studies, we outline a selection of the literature describing biological features of CTCs with an impact on their metastasis forming ability in different GI cancers.
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Affiliation(s)
- Simran Asawa
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland
| | - Manuel Nüesch
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland
| | - Ana Gvozdenovic
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland
| | - Nicola Aceto
- Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland.
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12
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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: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [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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13
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Ding L, Gosh A, Lee DJ, Emri G, Huss WJ, Bogner PN, Paragh G. Prognostic biomarkers of cutaneous melanoma. PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2022; 38:418-434. [PMID: 34981569 DOI: 10.1111/phpp.12770] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 12/02/2021] [Accepted: 12/30/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND/PURPOSE Melanomas account for only approximately 4% of diagnosed skin cancers in the United States but are responsible for the majority of deaths caused by skin cancer. Both genetic factors and ultraviolet (UV) radiation exposure play a role in the development of melanoma. Although melanomas have a strong propensity to metastasize when diagnosed late, melanomas that are diagnosed and treated early pose a low mortality risk. In particular, the identification of patients with increased metastatic risk, who may benefit from early adjuvant therapies, is crucial, especially given the advent of new melanoma treatments. However, the accuracy of classic clinical and histological variables, including the Breslow thickness, presence of ulceration, and lymph node status, might not be sufficient to identify such individuals. Thus, there is a need for the development of additional prognostic melanoma biomarkers that can improve early attempts to stratify melanoma patients and reliably identify high-risk subgroups with the aim of providing effective personalized therapies. METHODS In our current work, we discuss and assess emerging primary melanoma tumor biomarkers and prognostic circulating biomarkers. RESULTS Several promising biomarkers show prognostic value (eg, exosomal MIA (ie, melanoma inhibitory activity), serum S100B, AMLo signatures, and mRNA signatures); however, the scarcity of reliable data precludes the use of these biomarkers in current clinical applications. CONCLUSION Further research is needed on several promising biomarkers for melanoma. Large-scale studies are warranted to facilitate the clinical translation of prognostic biomarker applications for melanoma in personalized medicine.
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Affiliation(s)
- Liang Ding
- Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- Department of Pathology, Buffalo General Medical Center, State University of New York, Buffalo, New York, USA
| | - Alexandra Gosh
- Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Delphine J Lee
- Division of Dermatology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA
- Division of Dermatology, Department of Medicine, The Lundquist Institute, Torrance, California, USA
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Gabriella Emri
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Wendy J Huss
- Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Paul N Bogner
- Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Gyorgy Paragh
- Department of Dermatology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
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14
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Agnoletto C, Volinia S. Mitochondria dysfunction in circulating tumor cells. Front Oncol 2022; 12:947479. [PMID: 35992829 PMCID: PMC9386562 DOI: 10.3389/fonc.2022.947479] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/11/2022] [Indexed: 12/16/2022] Open
Abstract
Circulating tumor cells (CTCs) represent a subset of heterogeneous cells, which, once released from a tumor site, have the potential to give rise to metastasis in secondary sites. Recent research focused on the attempt to detect and characterize these rare cells in the circulation, and advancements in defining their molecular profile have been reported in diverse tumor species, with potential implications for clinical applications. Of note, metabolic alterations, involving mitochondria, have been implicated in the metastatic process, as key determinants in the transition of tumor cells to a mesenchymal or stemness-like phenotype, in drug resistance, and in induction of apoptosis. This review aimed to briefly analyse the most recent knowledge relative to mitochondria dysfunction in CTCs, and to envision implications of altered mitochondria in CTCs for a potential utility in clinics.
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Affiliation(s)
- Chiara Agnoletto
- Rete Oncologica Veneta (ROV), Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Stefano Volinia
- Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA), Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Biological and Chemical Research Centre (CNBCh UW), University of Warsaw, Warsaw, Poland
- Center of New Technologies, University of Warsaw, Warsaw, Poland
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15
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Yadav A, Kumar A, Siddiqui MH. Detection of circulating tumour cells in colorectal cancer: Emerging techniques and clinical implications. World J Clin Oncol 2021; 12:1169-1181. [PMID: 35070736 PMCID: PMC8716996 DOI: 10.5306/wjco.v12.i12.1169] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/15/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Despite several advances in oncological management of colorectal cancer, morbidity and mortality are still high and devastating. The diagnostic evaluation by endoscopy is cumbersome, which is uncomfortable to many. Because of the intra- and inter-tumour heterogeneity and changing tumour dynamics, which is continuous in nature, the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate. Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases. One of the keys to improving the outcome is early detection of cancer, ease of technology to detect with uniformity, and its therapeutic implications, which are yet to come. "Liquid biopsy" is currently the most recent area of interest in oncology, which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease. By using this approach, clinicians may be able to find out information about the tumour at a given time. Any of the following three types of sampling of biological material can be used in the "liquid biopsy". These are circulating tumour cells (CTCs), circulating tumour DNA, and exosomes. The most commonly studied amongst the three is CTCs. CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics. In this review, we will discuss various markers for CTCs, the core tools/techniques for detection, and also important findings of clinical studies in colorectal cancer and its clinical implications.
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Affiliation(s)
- Alka Yadav
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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16
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Chivu-Economescu M, Necula L, Matei L, Dragu D, Bleotu C, Diaconu CC. Clinical Applications of Liquid Biopsy in Gastric Cancer. Front Med (Lausanne) 2021; 8:749250. [PMID: 34651002 PMCID: PMC8505538 DOI: 10.3389/fmed.2021.749250] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 08/31/2021] [Indexed: 02/05/2023] Open
Abstract
Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, offering a less invasive and more convenient approach to obtain a time-point image of the tumor burden and its genomic profile. Samples collected from several body fluids, mostly blood, can be used to gain access to circulating tumor cells and DNA, non-coding RNAs, microRNAs, and exosomes, at any moment, offering a dynamic picture of the tumor. For patients with GC, the use of blood-based biopsies may be particularly beneficial since tissue biopsies are difficult to obtain and cause real distress to the patient. With advantages such as repeatability and minimal invasion, it is no wonder that the field of liquid biopsy has received tremendous attention. However, the abundance of studies, involving a wide range of assays with different principles, prevented for the moment the reproducibility of the results and therefore the translation into the clinic of liquid biopsy. In this review, we present the latest technical development and data on circulating biomarkers available through liquid biopsy in gastric cancer with an emphasis on their clinical utility in areas such as cancer screening, prognostic stratification, and therapeutic management.
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Affiliation(s)
- Mihaela Chivu-Economescu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Laura Necula
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
- Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Denisa Dragu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Coralia Bleotu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
| | - Carmen C. Diaconu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest, Romania
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17
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Pelizzaro F, Cardin R, Penzo B, Pinto E, Vitale A, Cillo U, Russo FP, Farinati F. Liquid Biopsy in Hepatocellular Carcinoma: Where Are We Now? Cancers (Basel) 2021; 13:2274. [PMID: 34068786 PMCID: PMC8126224 DOI: 10.3390/cancers13092274] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 04/30/2021] [Accepted: 05/06/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Diagnostic, prognostic, and predictive biomarkers are urgently needed in order to improve patient survival. Indeed, the most widely used biomarkers, such as alpha-fetoprotein (AFP), have limited accuracy as both diagnostic and prognostic tests. Liver biopsy provides an insight on the biology of the tumor, but it is an invasive procedure, not routinely used, and not representative of the whole neoplasia due to the demonstrated intra-tumoral heterogeneity. In recent years, liquid biopsy, defined as the molecular analysis of cancer by-products, released by the tumor in the bloodstream, emerged as an appealing source of new biomarkers. Several studies focused on evaluating extracellular vesicles, circulating tumor cells, cell-free DNA and non-coding RNA as novel reliable biomarkers. In this review, we aimed to provide a comprehensive overview on the most relevant available evidence on novel circulating biomarkers for early diagnosis, prognostic stratification, and therapeutic monitoring. Liquid biopsy seems to be a very promising instrument and, in the near future, some of these new non-invasive tools will probably change the clinical management of HCC patients.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (F.P.); (R.C.); (B.P.); (E.P.); (F.P.R.)
| | - Romilda Cardin
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (F.P.); (R.C.); (B.P.); (E.P.); (F.P.R.)
| | - Barbara Penzo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (F.P.); (R.C.); (B.P.); (E.P.); (F.P.R.)
| | - Elisa Pinto
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (F.P.); (R.C.); (B.P.); (E.P.); (F.P.R.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (A.V.); (U.C.)
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (F.P.); (R.C.); (B.P.); (E.P.); (F.P.R.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padua, Italy; (F.P.); (R.C.); (B.P.); (E.P.); (F.P.R.)
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18
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Ito H, Uragami N, Miyazaki T, Yang W, Issha K, Matsuo K, Kimura S, Arai Y, Tokunaga H, Okada S, Kawamura M, Yokoyama N, Kushima M, Inoue H, Fukagai T, Kamijo Y. Highly accurate colorectal cancer prediction model based on Raman spectroscopy using patient serum. World J Gastrointest Oncol 2020; 12:1311-1324. [PMID: 33250963 PMCID: PMC7667458 DOI: 10.4251/wjgo.v12.i11.1311] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/28/2020] [Accepted: 10/19/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.
AIM To develop a comprehensive, spontaneous, minimally invasive, label-free, blood-based CRC screening technique based on Raman spectroscopy.
METHODS We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC (12), rectal neuroendocrine tumor (2), colorectal adenoma (68), colorectal hyperplastic polyp (18), and others (84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.
RESULTS Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.
CONCLUSION For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.
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Affiliation(s)
- Hiroaki Ito
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Naoyuki Uragami
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | | | | | - Kenji Issha
- Fuji Technical Research Inc., Yokohama 220-6215, Japan
| | - Kai Matsuo
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Satoshi Kimura
- Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
| | - Yuji Arai
- Department of Clinical Laboratory, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Hiromasa Tokunaga
- Department of Clinical Laboratory, Showa University Hospital, Tokyo 142-8555, Japan, BML Inc., Tokyo 151-0051, Japan
| | - Saiko Okada
- Department of Clinical Laboratory, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Machiko Kawamura
- Department of Hematology, Saitama Cancer Center, Inamachi, Saitama 362-0806, Japan
| | - Noboru Yokoyama
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Miki Kushima
- Department of Pathology, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Takashi Fukagai
- Department of Urology, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
| | - Yumi Kamijo
- Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
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19
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Tsai WS, Hung WS, Wang TM, Liu H, Yang CY, Wu SM, Hsu HL, Hsiao YC, Tsai HJ, Tseng CP. Circulating tumor cell enumeration for improved screening and disease detection of patients with colorectal cancer. Biomed J 2020; 44:S190-S200. [PMID: 35292267 PMCID: PMC9068522 DOI: 10.1016/j.bj.2020.09.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/21/2020] [Accepted: 09/27/2020] [Indexed: 12/13/2022] Open
Abstract
Background The immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening and the serum carcinoembryonic antigen (CEA) assay for disease detection of CRC is associated with a high false-positive rate and a low detection sensitivity, respectively. There is an unmet need to define additional modalities to complement these assays. Different subsets of circulating tumor cells (CTCs) are present in the peripheral blood of cancer patients. Whether or not CTCs testing supplements these clinical assays and is valuable for patients with CRC was investigated. Methods CTCs were enriched from pre-operative patients with CRC (n = 109) and the non-cancerous controls (n = 65). CTCs expressing either epithelial cell adhesion molecule (EpCAM) or podoplanin (PDPN, the marker associated with poor cancer prognosis) were defined by immunofluorescence staining and were analyzed alone or in combination with iFOBT or serum CEA. Results Patients with early or advanced stage of CRC can be clearly identified and differentiated from the non-cancerous controls (p < 0.001) by EpCAM+-CTC or PDPN+-CTC count. The sensitivity and specificity of EpCAM+-CTCs was 85.3% and 78.5%, respectively, when the cutoff value was 23 EpCAM+-CTCs/mL of blood; and the sensitivity and specificity of PDPN+-CTCs was 78.0% and 75.4%, respectively, when the cutoff value was 7 PDPN+-CTCs/mL of blood. Combined analysis of iFOBT with the EpCAM+-CTC and PDPN+-CTC count reduced the false-positive rate of iFOBT from 56.3% to 18.8% and 23.4%, respectively. Combined analysis of serum CEA with the EpCAM+-CTC and PDPN+-CTC count increased the disease detection rate from 30.3% to 89.9% and 86.2%, respectively. Conclusion CTC testing could supplement iFOBT to improve CRC screening and supplement serum CEA assay for better disease detection of patients with CRC.
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20
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Okazaki M, Yamaguchi T, Tajima H, Fushida S, Ohta T. Platelet adherence to cancer cells promotes escape from innate immune surveillance in cancer metastasis. Int J Oncol 2020; 57:980-988. [PMID: 32945350 DOI: 10.3892/ijo.2020.5102] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 07/07/2020] [Indexed: 11/05/2022] Open
Abstract
The impacts of post‑operative abdominal infectious complications increase hematogenous distant metastasis and result in poor long‑term survival after curative resection. Even if curative resection can be performed, the presence of circulating tumor cells is affected. The liver, the most common site of metastases, is an important organ in innate immune surveillance. However, the molecular mechanisms of distant hematogenous metastasis are not yet fully known. Platelets are crucial components in the tumor microenvironment that function to promote tumor progression and metastasis. The purpose of this study was to identify the effect of platelets on escape from innate immune surveillance in post‑operative abdominal infectious complications. Platelet adherence was assessed by co‑culturing human pancreatic cancer cells including transforming growth factor (TGF‑β)‑treated BxPC‑3. CD44 isoform, transcription factors and epithelial‑mesenchymal transition markers were examined using western blotting. We also assessed whether cancer cells surrounded by activated platelets could escape from innate immune surveillance, using infectious and non‑infectious mouse models injected intraperitoneally with LPS. Platelets were found to preferentially adhere to mesenchymal cells rather than epithelial cells. BxPC‑3 epithelial cells showed upregulation of CD44‑variant and epithelial splicing regulatory protein 1 (ESRP‑1) expression. However, Panc‑1 mesenchymal cells and TGF‑β‑treated BxPC‑3 cells showed upregulation of CD44‑standard and zinc finger E‑box‑binding homeobox 1 (ZEB‑1) expression and a reduction in ESRP‑1. In the non‑infectious model, cancer cells were not found in the liver. In the infectious model, although epithelial cells without platelet adhesion were in an apoptotic state, mesenchymal cells showed many viable cancer cells surrounded by activated platelets. Cancer cells were suggested to have phenotypic plasticity through the switching of CD44 isoforms. Mesenchymal cells, which express CD44‑standard, could escape from immune surveillance by becoming surrounded by adhered activated platelets. Therefore, it may be necessary to administer antiplatelet agents to prevent distant hematogenous metastasis when post‑operative abdominal infectious complications occur.
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Affiliation(s)
- Mitsuyoshi Okazaki
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan
| | - Takahisa Yamaguchi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan
| | - Hidehiro Tajima
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan
| | - Tetsuo Ohta
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920‑8641, Japan
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21
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Kolenčík D, Shishido SN, Pitule P, Mason J, Hicks J, Kuhn P. Liquid Biopsy in Colorectal Carcinoma: Clinical Applications and Challenges. Cancers (Basel) 2020; 12:E1376. [PMID: 32471160 PMCID: PMC7352156 DOI: 10.3390/cancers12061376] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 05/16/2020] [Accepted: 05/25/2020] [Indexed: 12/24/2022] Open
Abstract
Colorectal carcinoma (CRC) is characterized by wide intratumor heterogeneity with general genomic instability and there is a need for improved diagnostic, prognostic, and therapeutic tools. The liquid biopsy provides a noninvasive route of sample collection for analysis of circulating tumor cells (CTCs) and genomic material, including cell-free DNA (cfDNA), as a complementary biopsy to the solid tumor tissue. The solid biopsy is critical for molecular characterization and diagnosis at the time of collection. The liquid biopsy has the advantage of longitudinal molecular characterization of the disease, which is crucial for precision medicine and patient-oriented treatment. In this review, we provide an overview of CRC and the different methodologies for the detection of CTCs and cfDNA, followed by a discussion on the potential clinical utility of the liquid biopsy in CRC patient care, and lastly, current challenges in the field.
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Affiliation(s)
- Drahomír Kolenčík
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic; (D.K.); (P.P.)
| | - Stephanie N. Shishido
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
| | - Pavel Pitule
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic; (D.K.); (P.P.)
| | - Jeremy Mason
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
- USC Institute of Urology, Catherine & Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - James Hicks
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
| | - Peter Kuhn
- Convergent Science Institute in Cancer, Michelson Center for Convergent Bioscience, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; (S.N.S.); (J.M.); (J.H.)
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22
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Nevel KS, DiStefano N, Lin X, Skakodub A, Ogilvie SQ, Reiner AS, Pentsova E, Boire A. A retrospective, quantitative assessment of disease burden in patients with leptomeningeal metastases from non-small-cell lung cancer. Neuro Oncol 2020; 22:675-683. [PMID: 32352148 PMCID: PMC7229251 DOI: 10.1093/neuonc/noz208] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Improvements in detection and molecular characterization of leptomeningeal metastasis from lung cancer (LC-LM) coupled with cerebrospinal fluid (CSF)-penetrating targeted therapies have altered disease management. A barrier to formal study of these therapies in LM is quantification of disease burden. Also, outcomes of patients with targetable mutations in LC-LM are not well defined. This study employs molecular and radiographic measures of LM disease burden and correlates these with outcome. METHODS We reviewed charts of 171 patients with LC-LM treated at Memorial Sloan Kettering. A subset had MRI and CSF studies available. Radiographic involvement (n = 76) was scored by number of gadolinium-enhancing sites in 8 locations. CSF studies included cytopathology, circulating tumor cell (CTC) quantification (n = 16), and cell-free DNA (cfDNA) analysis (n = 21). Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies. RESULTS Median overall survival was 4.2 months (95% CI: 3.6-4.9); 84 patients (49%) harbored targetable mutations. Among bevacizumab-naïve patients with MRI and CSF cytology at time of LC-LM diagnosis, extent of radiographic involvement correlated with risk of death (hazard ratio [HR]: 1.16; 95% CI: 1.02-1.33; P = 0.03), as did CSF CTC (HR: 3.39, 95% CI: 1.01-11.37; P = 0.048) and CSF cfDNA concentration (HR: 2.58; 95% CI: 0.94-7.05; P = 0.06). Those without a targetable mutation were almost 50% more likely to die (HR: 1.49; 95% CI: 1.06-2.11; P = 0.02). CONCLUSIONS Extent of radiographic involvement and quantification of CSF CTC and cfDNA show promise as prognostic indicators. These findings support molecular characterization and staging for clinical management, prognostication, and clinical trial stratification of LC-LM.
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Affiliation(s)
- Kathryn S Nevel
- Department of Neurology, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Natalie DiStefano
- Brain Tumor Center, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Xuling Lin
- Department of Neurology, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Anna Skakodub
- Department of Neurology, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Shahiba Q Ogilvie
- Brain Tumor Center, New York, New York
- Department of Neurosurgery, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Anne S Reiner
- Department of Epidemiology and Biostatistics, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Elena Pentsova
- Department of Neurology, New York, New York
- Brain Tumor Center, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
| | - Adrienne Boire
- Department of Neurology, New York, New York
- Brain Tumor Center, New York, New York
- Human Oncology and Pathogenesis Program, New York, New York
- Memorial Sloan Kettering Cancer Center, New York, New York
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23
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Quinchia J, Echeverri D, Cruz-Pacheco AF, Maldonado ME, Orozco J. Electrochemical Biosensors for Determination of Colorectal Tumor Biomarkers. MICROMACHINES 2020; 11:E411. [PMID: 32295170 PMCID: PMC7231317 DOI: 10.3390/mi11040411] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/13/2020] [Accepted: 03/17/2020] [Indexed: 12/15/2022]
Abstract
The accurate determination of specific tumor markers associated with cancer with non-invasive or minimally invasive procedures is the most promising approach to improve the long-term survival of cancer patients and fight against the high incidence and mortality of this disease. Quantification of biomarkers at different stages of the disease can lead to an appropriate and instantaneous therapeutic action. In this context, the determination of biomarkers by electrochemical biosensors is at the forefront of cancer diagnosis research because of their unique features such as their versatility, fast response, accurate quantification, and amenability for multiplexing and miniaturization. In this review, after briefly discussing the relevant aspects and current challenges in the determination of colorectal tumor markers, it will critically summarize the development of electrochemical biosensors to date to this aim, highlighting the enormous potential of these devices to be incorporated into the clinical practice. Finally, it will focus on the remaining challenges and opportunities to bring electrochemical biosensors to the point-of-care testing.
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Affiliation(s)
- Jennifer Quinchia
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
| | - Danilo Echeverri
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
| | - Andrés Felipe Cruz-Pacheco
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
| | - María Elena Maldonado
- Grupo Impacto de los Componentes Alimentarios en la Salud, School of Dietetics and Human Nutrition, University of Antioquia, A.A. 1226, Medellín 050010, Colombia;
| | - Jahir Orozco
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
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24
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de Miguel Pérez D, Rodriguez Martínez A, Ortigosa Palomo A, Delgado Ureña M, Garcia Puche JL, Robles Remacho A, Exposito Hernandez J, Lorente Acosta JA, Ortega Sánchez FG, Serrano MJ. Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients. Sci Rep 2020; 10:3974. [PMID: 32132553 PMCID: PMC7055306 DOI: 10.1038/s41598-020-60212-1] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 11/05/2019] [Indexed: 12/11/2022] Open
Abstract
Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC.
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Affiliation(s)
- Diego de Miguel Pérez
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain.,Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain
| | - Alba Rodriguez Martínez
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain.,Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain
| | - Alba Ortigosa Palomo
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain
| | - Mayte Delgado Ureña
- Integral Oncology Division, University Hospital Virgen de las Nieves, IBS Granada, Instituto de Investigación Biosanitaria de Granada, 18012, Granada, Spain
| | - Jose Luis Garcia Puche
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain.,Integral Oncology Division, University Hospital Virgen de las Nieves, IBS Granada, Instituto de Investigación Biosanitaria de Granada, 18012, Granada, Spain
| | - Agustín Robles Remacho
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain
| | - José Exposito Hernandez
- Integral Oncology Division, University Hospital Virgen de las Nieves, IBS Granada, Instituto de Investigación Biosanitaria de Granada, 18012, Granada, Spain
| | - Jose Antonio Lorente Acosta
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain.,Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain
| | - Francisco Gabriel Ortega Sánchez
- Balearic Islands Health Research Institute (IdISBa), 07010, Palma de Mallorca, Spain. .,Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
| | - Ma Jose Serrano
- GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Avenida de la Ilustración 114, 18016, Granada, Spain. .,Integral Oncology Division, University Hospital Virgen de las Nieves, IBS Granada, Instituto de Investigación Biosanitaria de Granada, 18012, Granada, Spain.
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25
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Current applications and challenges of circulating tumor DNA (ctDNA) in squamous cell carcinoma of the head and neck (SCCHN). Cancer Treat Rev 2020; 85:101992. [PMID: 32092618 DOI: 10.1016/j.ctrv.2020.101992] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 02/12/2020] [Indexed: 12/21/2022]
Abstract
Liquid biopsies (LB) are emerging in the oncology field, with promising data as new diagnostic, prognostic and treatment-monitoring tools. Squamous cell carcinoma of the head and neck (SCCHN) is a heterogenous disease and many challenges remain to improve patient outcomes. Liquid biopsy could be of interest at different stages of SCCHN disease, including better screening to diagnose more patients at an early stage, early detection of relapse after curative treatment, and the implementation of precision medicine. As LB is very attractive by the ease of sampling, this field is moving fast. Therefore, it is important to be aware of the potential applications but also the limitations of these new tools in regards to technical aspects and interpretation of the data. In this review, we will first give an overview of potential clinical applications and technical challenges of circulating tumor DNA (ctDNA) and then focus on current available data of ctDNA in SCCHN. Although the literature on ctDNA analysis for SCCHN is scarce compared to other tumors, preliminary results seem to hold promise for the future, including the detection of minimal residual disease or the detection of potentially targetable events through liquid biopsy. Prospective liquid-biopsy driven clinical trials are needed to validate its clinical relevance.
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26
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ATİLLA MK, AVCI B, İRKILATA L, AYDIN M, BİTKİN A, KELEŞ M, YÜCEL İ, ULUBAY M. Does transrectal ultrasonography-guided biopsy of the prostate lead to possible further metastasis via circulating tumor cells? Turk J Med Sci 2019; 49:1701-1706. [PMID: 31655516 PMCID: PMC7518687 DOI: 10.3906/sag-1904-58] [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: 04/08/2019] [Accepted: 10/02/2019] [Indexed: 11/20/2022] Open
Abstract
Background/aim We evaluate whether transrectal ultrasonography (TRUS)-guided prostate biopsy might lead to spillage of tumor cells into peripheral blood as a result of disruption of the epithelial barrier and ultimately result in metastasis. Materials and methods Eighty-eight patients underwent TRUS-guided prostate needle biopsy due to prostate-specific antigen (PSA) increase or abnormal digital rectal examination at the Samsun Research and Training Hospital (Samsun, Turkey) between April 2016 and September 2018. Approximately 10 mL of whole blood was collected from patients before, 1 week after, and 1 month after biopsy. Samples were analyzed for CD117 positivity and prostate-specific membrane antigen (PSMA) levels using flow cytometry. Patients with pathologically determined prostate cancer and without CD117 positivity before biopsy were included in the study. The study group thus consisted of 55 patients. Results Subjects’ PSA levels ranged from 2.3 to 40.0 ng/mL (median: 7.9 ng/mL), and their Gleason score was a median of 7 (range: 5–9). PSMA levels ranged between 9.3 ng/mL and 118.5 ng/mL and CD117 antigen levels between 0 and 5. We detected no CD117- positive cells in blood samples collected 7 days or 1 month after biopsy. Conclusion We detected no circulating tumor cells in the peripheral circulation following biopsy. Prostate needle biopsy seems to be a safe method in terms of spillage of tumor cells into blood circulation as a possible cause of further metastasis.
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Affiliation(s)
| | - Bahattin AVCI
- Department of Biochemistry, School of Medicine, Ondokuz Mayıs University, SamsunTurkey
| | - Lokman İRKILATA
- Department of Urology, Samsun Research and Training Hospital, SamsunTurkey
| | - Mustafa AYDIN
- Department of Urology, Samsun Research and Training Hospital, SamsunTurkey
| | - Alper BİTKİN
- Department of Urology, Samsun Research and Training Hospital, SamsunTurkey
| | - Mevlüt KELEŞ
- Department of Urology, Samsun Research and Training Hospital, SamsunTurkey
| | - İnci YÜCEL
- Department of Pathology, Samsun Research and Training Hospital, SamsunTurkey
| | - Mahmut ULUBAY
- Department of Urology, Samsun Research and Training Hospital, SamsunTurkey
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27
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Pan Y, Long W, Liu Q. Current Advances and Future Perspectives of Cerebrospinal Fluid Biopsy in Midline Brain Malignancies. Curr Treat Options Oncol 2019; 20:88. [PMID: 31784837 DOI: 10.1007/s11864-019-0689-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OPINION STATEMENT Malignancies arising in midline brain structures, including lymphomas, teratomas, germinomas, diffuse midline gliomas, and medulloblastomas typically respond to systemic therapies, and excessive surgical excision can result in serious complications, so that total surgical removal is not routinely performed. Identifying tumor specific biomarkers that can facilitate diagnosis at early stage and allow for dynamic surveillance of the tumor is of great clinical importance. However, existing standard methods for biopsy of these brain neoplasms are high risk, time consuming, and costly. Thus, less invasive and more rapid diagnosis tests are urgently needed to detect midline brain malignancies. Currently, tools for cerebrospinal biopsy of midline brain malignancies mainly include circulating tumor DNA, circulating tumor cells, and extracellular vesicles. Circulating tumor DNA achieved minimally invasive biopsy in several brain malignancies and has advantages in detecting tumor-specific mutations. In the field of tumor heterogeneity, circulating tumor cells better reflect the genome of tumors than surgical biopsy specimens. They can be applied for the diagnosis of leptomeningeal metastasis. Extracellular vesicles contain lots of genetic information about cancer cells, so they have potential in finding therapeutic targets and studying tumor invasion and metastasis.
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Affiliation(s)
- Yimin Pan
- Department of Neurosurgery in Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Wenyong Long
- Department of Neurosurgery in Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Qing Liu
- Department of Neurosurgery in Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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28
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Lee SW, Chen YW, Kuan EC, Lan MY. Dual-function nanostructured platform for isolation of nasopharyngeal carcinoma circulating tumor cells and EBV DNA detection. Biosens Bioelectron 2019; 142:111509. [PMID: 31344600 DOI: 10.1016/j.bios.2019.111509] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 07/11/2019] [Accepted: 07/12/2019] [Indexed: 12/19/2022]
Abstract
Circulating tumor cells (CTCs) and plasma levels of Epstein-Barr virus (EBV) DNA are sensitive prognostic tools for monitoring disease status in nasopharyngeal carcinoma (NPC) patients. Herein, we introduce a novel and low-cost platform for capturing CTCs, the Si nanowires/microscale pyramids (NWs/MPs) hierarchical substrate, which could capture NPC cells in vitro and also detect EBV DNA at very low concentrations. In this study, Si NWs/MPs hierarchical substrates with varying wire length were fabricated using a metal-assisted chemical etching method. Anti-EpCAM antibodies were further conjugated on the substrate for capturing NPC CTCs in vitro. Capture efficiency was evaluated using immunofluorescence and scanning electronic microscopy (SEM) was utilized to understand cell morphology. The Si NWs/MPs substrate was also transformed into a Surface enhanced Raman scattering (SERS) substrate by coating with Ag nanoparticles (AgNPs) for detection of EBV DNA by Raman spectroscopy. The results demonstrated that Si NWs/MPs with 20 min of etch time had the best capturing performance. Additionally, SEM observations revealed good contact of CTCs with Si NWs/MPs substrates. Moreover, the AgNPs-coated NWs/MPs substrate was shown to be a sensitive EBV DNA detector, by which the DNA detection limit can reach up to 10-13M. In conclusion, the Si NWs/MPs platform not only exhibits superior cell capturing ability, but also can sensitively detect EBV DNA at very low concentrations. This platform has great potential to become a promising diagnostic tool for monitoring disease status and prognostication of NPC patients.
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Affiliation(s)
- Sheng-Wei Lee
- Institute of Materials Science and Engineering, National Central University, Taoyuan City 32001, Taiwan; Department of Materials Science and Engineering, University of California, Irvine, Orange, CA 92697, USA.
| | - Yi-Wei Chen
- Institute of Materials Science and Engineering, National Central University, Taoyuan City 32001, Taiwan
| | - Edward C Kuan
- Department of Otolaryngology-Head and Neck Surgery, University of California, Irvine, Orange, CA 92868, USA.
| | - Ming-Ying Lan
- Division of Rhinology, Department of Otolaryngology Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, 11217, Taiwan; School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
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Wang HM, Wu MH, Chang PH, Lin HC, Liao CD, Wu SM, Hung TM, Lin CY, Chang TC, Tzu-Tsen Y, Hsieh JCH. The change in circulating tumor cells before and during concurrent chemoradiotherapy is associated with survival in patients with locally advanced head and neck cancer. Head Neck 2019; 41:2676-2687. [PMID: 30903634 DOI: 10.1002/hed.25744] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 03/07/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND This study aimed to evaluate the role of baseline circulating tumor cells (CTCs) before and during concurrent chemoradiotherapy and attempted to determine the impacts of CTCs on the outcomes in patients with head and neck squamous cell carcinoma. METHODS CTCs were detected using a negative selection strategy and flow cytometry protocol. RESULTS We observed a significant correlation between baseline CTCs and staging (P = 0.001). The CTC counts were significantly reduced within 2-4 weeks in 47 concurrent chemoradiotherapy responders (P < 0.001). Change of CTC counts correlates with progression-free survival (PFS, P = 0.01) and overall survival (OS, P = 0.01). CTC decline status was an independent prognostic factor in PFS (P = 0.03) and OS (P = 0.05) in multivariate analyses. CONCLUSION In chemoradiotherapy responders, CTCs are significantly reduced. CTC decline within the first month indicates a longer PFS and OS, suggesting that the dynamics of CTCs could be more important than CTC number alone.
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Affiliation(s)
- Hung-Ming Wang
- Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Min-Hsien Wu
- Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan.,Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.,Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan
| | - Pei-Hung Chang
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan and Chang Gung University, Taoyuan, Taiwan.,Cancer Center, Chang Gung Memorial Hospital, Keelung, and Chang Gung University, Taoyuan, Taiwan
| | - Hung-Chi Lin
- Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Chun-Da Liao
- Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Sheng-Min Wu
- Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Tsung-Min Hung
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chine-Yu Lin
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tung-Chieh Chang
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yen Tzu-Tsen
- Molecular Imaging Center, Linkou Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan.,Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Jason Chia-Hsun Hsieh
- Circulating Tumor Cell Lab, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taoyuan, Taiwan.,Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan
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30
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Paolillo C, Londin E, Fortina P. Single-Cell Genomics. Clin Chem 2019; 65:972-985. [PMID: 30872376 DOI: 10.1373/clinchem.2017.283895] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 01/28/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Single-cell genomics is an approach to investigate cell heterogeneity and to identify new molecular features correlated with clinical outcomes. This approach allows identification of the complexity of cell diversity in a sample without the loss of information that occurs when multicellular or bulk tissue samples are analyzed. CONTENT The first single-cell RNA-sequencing study was published in 2009, and since then many more studies and single-cell sequencing methods have been published. These studies have had a major impact on several fields, including microbiology, neurobiology, cancer, and developmental biology. Recently, improvements in reliability and the development of commercial single-cell isolation platforms are opening the potential of this technology to the clinical laboratory. SUMMARY In this review we provide an overview of the current state of single-cell genomics. We describe opportunities in clinical research and medical applications.
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Affiliation(s)
- Carmela Paolillo
- Division of Precision and Computational Diagnostics, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Eric Londin
- Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
| | - Paolo Fortina
- Department of Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA; .,Department of Molecular Medicine, Sapienza University, Rome, Italy
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31
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Mann J, Reeves HL, Feldstein AE. Liquid biopsy for liver diseases. Gut 2018; 67:2204-2212. [PMID: 30177542 DOI: 10.1136/gutjnl-2017-315846] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 07/24/2018] [Accepted: 07/25/2018] [Indexed: 12/12/2022]
Abstract
With the growing number of novel therapeutic approaches for liver diseases, significant research efforts have been devoted to the development of liquid biopsy tools for precision medicine. This can be defined as non-invasive reliable biomarkers that can supplement and eventually replace the invasive liver biopsy for diagnosis, disease stratification and monitoring of response to therapeutic interventions. Similarly, detection of liver cancer at an earlier stage of the disease, potentially susceptible to curative resection, can be critical to improve patient survival. Circulating extracellular vesicles, nucleic acids (DNA and RNA) and tumour cells have emerged as attractive liquid biopsy candidates because they fulfil many of the key characteristics of an ideal biomarker. In this review, we summarise the currently available information regarding these promising and potential transformative tools, as well as the issues still needed to be addressed for adopting various liquid biopsy approaches into clinical practice. These studies may pave the way to the development of a new generation of reliable, mechanism-based disease biomarkers.
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Affiliation(s)
- Jelena Mann
- Newcastle Fibrosis Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Helen L Reeves
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
| | - Ariel E Feldstein
- Department of Pediatrics, University of California, San Diego, California, USA
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32
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Yang C, Shi D, Wang S, Wei C, Zhang C, Xiong B. Prognostic value of pre- and post-operative circulating tumor cells detection in colorectal cancer patients treated with curative resection: a prospective cohort study based on ISET device. Cancer Manag Res 2018; 10:4135-4144. [PMID: 30323669 PMCID: PMC6177518 DOI: 10.2147/cmar.s176575] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background Circulating tumor cells (CTCs) have been regarded as a promising biomarker for colorectal cancer (CRC); however, the prognostic value of post-operative (op) CTCs is still unclear. This study aimed to compare the recurrence prediction value of pre- and post-op CTCs in CRC patients treated with curative resection. Patients and methods Consecutive CRC patients treated with curative resection from January 2014 to March 2015 were identified. CTCs from 2.5 mL peripheral blood were enumerated with an ISETdevice-CTCBIOPSY® before and after surgery. Based on the status of pre- and post-op CTCs, the included patients were grouped into four cohorts: pre- and post-op CTCs−, pre-op CTCs− but post-op CTCs+, pre-op CTCs+ but post-op CTCs−, and pre- and post-op CTCs+. The 3-year recurrence-free survival (RFS) rate of patients was analyzed. Results A total of 138 patients (79 [57.2%] male; median age=62 [43–75] years) were enrolled. Patients with pre-op CTCs− had a 19.2% higher 3-year RFS rate (86.2%) than the combined cohorts with pre-op CTCs+ (67.0%) (P=0.038). Patients with post-op CTCs+ had aa 25.6% lower 3-year RFS rate (57.1%) than the combined cohorts with post-op CTCs− (82.7%) (P=0.001). Moreover, patients with pre- and post-op CTCs+ had a 25.1% lower 3-year RFS rate (53.8%) than patients with pre-op CTCs+ but post-op CTCs− (78.9%) (P=0.004). Multivariate analyses confirmed that post-op CTCs+ (HR=2.82, 95% CI=1.39–5.75, P=0.004), but not but pre-op CTCs+ (HR=2.17, 95% CI=0.75–6.31, P=0.153), was independently associated with shorter 3-year RFS rate. Conclusion Post-op CTCs+, but not pre-op CTCs+, is an independent indicator of poor prognosis for CRC patients treated with curative resection. Patients with post-op CTCs+ have a higher risk of recurrence those with pre-op CTCs+. Evaluation of post-op, rather than pre-op, CTCs is warranted.
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Affiliation(s)
- Chaogang Yang
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China, .,Hubei Key Laboratory of Tumor Biological Behaviors, Hubei, People's Republic of China, .,Hubei Cancer Clinical Study Center, Wuhan, Hubei, People's Republic of China,
| | - Dongdong Shi
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China, .,Hubei Key Laboratory of Tumor Biological Behaviors, Hubei, People's Republic of China, .,Hubei Cancer Clinical Study Center, Wuhan, Hubei, People's Republic of China,
| | - Shuyi Wang
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China, .,Hubei Key Laboratory of Tumor Biological Behaviors, Hubei, People's Republic of China, .,Hubei Cancer Clinical Study Center, Wuhan, Hubei, People's Republic of China,
| | - Chen Wei
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China, .,Hubei Key Laboratory of Tumor Biological Behaviors, Hubei, People's Republic of China, .,Hubei Cancer Clinical Study Center, Wuhan, Hubei, People's Republic of China,
| | - Chunxiao Zhang
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China, .,Hubei Key Laboratory of Tumor Biological Behaviors, Hubei, People's Republic of China, .,Hubei Cancer Clinical Study Center, Wuhan, Hubei, People's Republic of China,
| | - Bin Xiong
- Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China, .,Hubei Key Laboratory of Tumor Biological Behaviors, Hubei, People's Republic of China, .,Hubei Cancer Clinical Study Center, Wuhan, Hubei, People's Republic of China,
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Joosse SA, Souche FR, Babayan A, Gasch C, Kerkhoven RM, Ramos J, Fabre JM, Riethdorf S, König A, Wikman H, Alix-Panabières C, Pantel K. Chromosomal Aberrations Associated with Sequential Steps of the Metastatic Cascade in Colorectal Cancer Patients. Clin Chem 2018; 64:1505-1512. [PMID: 30030273 DOI: 10.1373/clinchem.2018.289819] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 07/02/2018] [Indexed: 02/02/2023]
Abstract
BACKGROUND Genomic information can help to identify colorectal tumors with high and low metastatic potential, thereby improving prediction of benefit of local and/or systemic treatment. Here we investigated chromosomal aberrations in relation to the different stages of the metastatic cascade: dissemination of tumor cells into the mesenteric vein, metastatic outgrowth in the liver, intravasation of the peripheral blood circulation, and development of further distant metastasis. METHODS Peripheral and mesenteric blood from colorectal cancer patients (n = 72) were investigated for circulating tumor cells, and DNA extracted from their primary tumors was subjected to array comparative genomic hybridization profiling. The results were validated with an independent set of primary colorectal tumors (n = 53) by quantitative reverse transcription PCR. RESULTS Mesenteric intravasation and liver metastasis were correlated with losses of chromosomes 16p (72%), 16q (27%), and 19 (54%), gain along 1q31 (45%) and 20q (60%), tumor cell infiltration into the peripheral blood circulation, and further distant metastasis with gain of chromosome 8q (59%) and 12 (47%, P < 0.01). Chromosome 12 gain was associated with poor overall survival in the initial (2.8 vs >7 years) and validation cohort (3.3 vs >6 years). The prospective study presented here is a hypothesis-generating study and confirmation with larger cohorts is required. CONCLUSIONS This is the first study that investigated colorectal cancer in its different stages of metastasis in correlation with copy number changes of the primary tumor. This information might be helpful to identify patients with limited metastatic spread who may profit from liver metastasis resection and may lead to the discovery of new therapeutic targets.Microarray data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE82228.
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Affiliation(s)
- Simon A Joosse
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - François-Régis Souche
- Department of Digestive Surgery, University Medical Center Montpellier, Montpellier, France
| | - Anna Babayan
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christin Gasch
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ron M Kerkhoven
- Genomics Core Facility, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Jeanne Ramos
- Laboratory of Pathology, University Medical Center Montpellier, Montpellier, France
| | - Jean-Michel Fabre
- Department of Digestive Surgery, University Medical Center Montpellier, Montpellier, France
| | - Sabine Riethdorf
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alexandra König
- Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Harriet Wikman
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Catherine Alix-Panabières
- Laboratory of Rare Human Circulating Cells, Department of Pathology and Oncobiology, University Medical Centre Montpellier, University of Montpellier EA2415 - Help for personalized Decision: Methodological Aspects, Montpellier, France
| | - Klaus Pantel
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
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Bracht JWP, Mayo-de-Las-Casas C, Berenguer J, Karachaliou N, Rosell R. The Present and Future of Liquid Biopsies in Non-Small Cell Lung Cancer: Combining Four Biosources for Diagnosis, Prognosis, Prediction, and Disease Monitoring. Curr Oncol Rep 2018; 20:70. [PMID: 30030656 DOI: 10.1007/s11912-018-0720-z] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW Liquid biopsies have potential as tools for diagnosis, prognosis, and prediction of response to therapy. Herein, we will extensively review four liquid biosources, tumor-educated platelets (TEPs), cell-free DNA (cfDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) and we will clarify their optimal application in non-small cell lung cancer (NSCLC) diagnosis and therapy. RECENT FINDINGS Liquid biopsies are a minimally invasive alternative to tissue biopsies-especially important in NSCLC patients-since tumor tissue is often unavailable or insufficient for complete genetic analysis. The main advantages of liquid biopsies include the possibility for repeated sampling, the lower cost, and the fact that they can reflect the complete molecular status of the patient better than a single-site biopsy. This is specifically important for lung adenocarcinoma patients since the detection of specific genetic alterations can predict response to targeted therapies. Molecular analysis is currently cardinal for therapy decision-making and disease monitoring in lung cancer patients. Liquid biopsies can make easier our daily clinical practice and if prospectively tested and validated may serve as a means for lung cancer early detection.
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Affiliation(s)
| | - Clara Mayo-de-Las-Casas
- Pangaea Oncology, Laboratory of Molecular Biology, Quirón-Dexeus University Institute, Sabino Arana 5-19, 08028, Barcelona, Spain
| | - Jordi Berenguer
- Pangaea Oncology, Laboratory of Molecular Biology, Quirón-Dexeus University Institute, Sabino Arana 5-19, 08028, Barcelona, Spain
| | - Niki Karachaliou
- Pangaea Oncology, Laboratory of Molecular Biology, Quirón-Dexeus University Institute, Sabino Arana 5-19, 08028, Barcelona, Spain. .,Instituto Oncológico Dr Rosell (IOR), University Hospital Sagrat Cor, QuironSalud Group, Viladomat 288, 08029, Barcelona, Spain.
| | - Rafael Rosell
- Pangaea Oncology, Laboratory of Molecular Biology, Quirón-Dexeus University Institute, Sabino Arana 5-19, 08028, Barcelona, Spain. .,Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Carretera de Canyet, s/n, 08916, Badalona, Barcelona, Spain. .,Institut d'Investigació en Ciències Germans Trias i Pujol, Camí de les Escoles, s/n, 08916, Badalona, Barcelona, Spain. .,Instituto Oncológico Dr Rosell (IOR), Quirón-Dexeus University Institute, Sabino Arana 5-19, 08028, Barcelona, Spain.
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Nevel KS, Wilcox JA, Robell LJ, Umemura Y. The Utility of Liquid Biopsy in Central Nervous System Malignancies. Curr Oncol Rep 2018; 20:60. [PMID: 29876874 DOI: 10.1007/s11912-018-0706-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Liquid biopsy is a sampling of tumor cells or tumor nucleotides from biofluids. This review explores the roles of liquid biopsy for evaluation and management of patients with primary and metastatic CNS malignancies. RECENT FINDINGS Circulating tumor cell (CTC) detection has emerged as a relatively sensitive and specific tool for diagnosing leptomeningeal metastases. Circulating tumor DNA (ctDNA) detection can effectively demonstrate genetic markup of CNS tumors in the cerebrospinal fluid, though its role in managing CNS malignancies is less well-defined. The value of micro RNA (miRNA) detection in CNS malignancies is unclear at this time. Current standard clinical tools for the diagnosis and monitoring of CNS malignancies have limitations, and liquid biopsy may help address clinical practice and knowledge gaps. Liquid biopsy offers exciting potential for the diagnosis, prognosis, and treatment of CNS malignancies, but each modality needs to be studied in large prospective trials to better define their use.
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Affiliation(s)
- Kathryn S Nevel
- Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Jessica A Wilcox
- Department of Neurology, NewYork-Presbyterian Hospital, Weill Cornell Medical Center, 520 E 70th St, Starr Pavilion 607, New York, NY, 10021, USA
| | - Lindsay J Robell
- Department of Neurology, University of Michigan, 1914 Taubman Center, 1500 E. Medical Center Dr., SPC 5316, Ann Arbor, MI, 48109-5316, USA
| | - Yoshie Umemura
- Department of Neurology, University of Michigan, 1914 Taubman Center, 1500 E. Medical Center Dr., SPC 5316, Ann Arbor, MI, 48109-5316, USA.
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36
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Gaiser MR, von Bubnoff N, Gebhardt C, Utikal JS. Liquid Biopsy zur Überwachung von Melanompatienten. J Dtsch Dermatol Ges 2018; 16:405-416. [DOI: 10.1111/ddg.13461_g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 10/21/2017] [Indexed: 01/03/2023]
Affiliation(s)
- Maria Rita Gaiser
- Klinische Kooperationseinheit Klinische Kooperationseinheit Dermatoonkologie des Deutschen; Krebsforschungszentrums (DKFZ); Heidelberg Deutschland
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Mannheim, Ruprecht-Karls-Universität Heidelberg; Mannheim Deutschland
| | - Nikolas von Bubnoff
- Klinik für Hämatologie; Onkologie und Stammzelltransplantation; Universitätsklinikum Freiburg; Deutschland
- Deutsches Konsortium für Translationale Krebsforschung (DKTK); Deutsches Krebsforschungszentrum (DKFZ); Heidelberg Deutschland
| | - Christoffer Gebhardt
- Klinische Kooperationseinheit Klinische Kooperationseinheit Dermatoonkologie des Deutschen; Krebsforschungszentrums (DKFZ); Heidelberg Deutschland
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Mannheim, Ruprecht-Karls-Universität Heidelberg; Mannheim Deutschland
| | - Jochen Sven Utikal
- Klinische Kooperationseinheit Klinische Kooperationseinheit Dermatoonkologie des Deutschen; Krebsforschungszentrums (DKFZ); Heidelberg Deutschland
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Mannheim, Ruprecht-Karls-Universität Heidelberg; Mannheim Deutschland
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Jain D, Roy-Chowdhuri S. Molecular Pathology of Lung Cancer Cytology Specimens: A Concise Review. Arch Pathol Lab Med 2018; 142:1127-1133. [PMID: 29547001 DOI: 10.5858/arpa.2017-0444-ra] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT - There has been a paradigm shift in the understanding of molecular pathogenesis of lung cancer. A number of oncogenic drivers have been identified in non-small cell lung carcinoma, such as the epidermal growth factor receptor ( EGFR) mutation and anaplastic lymphoma kinase ( ALK) gene rearrangement. Because of the clinical presentation at an advanced stage of disease in non-small cell lung carcinoma patients, the use of minimally invasive techniques is preferred to obtain a tumor sample for diagnosis. These techniques include image-guided biopsies and fine-needle aspirations, and frequently the cytology specimen may be the only tissue sample available for the diagnosis and molecular testing for these patients. OBJECTIVE - To review the current literature and evaluate the role of cytology specimens in lung cancer mutation testing. We reviewed the types of specimens received in the laboratory, specimen processing, the effect of preanalytic factors on downstream molecular studies, and the commonly used molecular techniques for biomarker testing in lung cancer. DATA SOURCES - PubMed and Google search engines were used to review the published literature on the topic. CONCLUSIONS - Mutation testing is feasible on a variety of cytologic specimen types and preparations. However, a thorough understanding of the cytology workflow for the processing of samples and appropriate background knowledge of the molecular tests are necessary for triaging, and optimum use of these specimens is necessary to guide patient management.
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Affiliation(s)
| | - Sinchita Roy-Chowdhuri
- From the Department of Pathology, All India Institute of Medical Sciences, New Delhi (Dr Jain); and the Division of Pathology and Laboratory Medicine, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston (Dr Roy-Chowdhuri)
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Gaiser MR, von Bubnoff N, Gebhardt C, Utikal JS. Liquid biopsy to monitor melanoma patients. J Dtsch Dermatol Ges 2018. [PMID: 29512873 DOI: 10.1111/ddg.13461] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression. Consequently, reliable methods for monitoring disease progression or treatment resistance are necessary. Localized and advanced cancers may generate circulating tumor cells and circulating tumor DNA (ctDNA) that can be detected and quantified from peripheral blood samples (liquid biopsy). For melanoma patients, liquid biopsy results may be useful as novel predictive biomarkers to guide therapeutic decisions, particularly in the context of mutation-based targeted therapies. The challenges of using liquid biopsy include strict criteria for the phenotypic nature of circulating MM cells or their fragments and the instability of ctDNA in blood. The limitations of liquid biopsy in routine diagnostic testing are discussed in this review.
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Affiliation(s)
- Maria Rita Gaiser
- Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
| | - Nikolas von Bubnoff
- Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Germany.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christoffer Gebhardt
- Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
| | - Jochen Sven Utikal
- Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
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Suh YS, Joung JY, Kim SH, Seo HK, Chung J, Lee KH. Establishment and Application of Prostate Cancer Circulating Tumor Cells in the Era of Precision Medicine. BIOMED RESEARCH INTERNATIONAL 2017; 2017:7206307. [PMID: 29230413 PMCID: PMC5694577 DOI: 10.1155/2017/7206307] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Accepted: 08/27/2017] [Indexed: 11/17/2022]
Abstract
Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC. Liquid biopsy using CTCs has been gaining attention as a minimal invasive tool for investigation of biomarkers and for prognosis and assessment of response to therapies in patients with PC. Because of the lower invasiveness of liquid biopsy using CTCs, it can be performed more frequently; accordingly, personalized disease status can be successively determined at serial time points. CTC analysis enables detection of genomic alterations, which is drug-targetable, and it is a potential tool for monitoring response to therapeutic agents in patients with PC. This review focuses on the characteristics, technologies for analysis, and advantages and disadvantages of CTCs as a liquid biopsy tool and their application in PC. Finally, we propose future directions of CTCs.
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Affiliation(s)
- Yoon Seok Suh
- Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Jae Young Joung
- Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Sung Han Kim
- Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Ho Kyung Seo
- Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Jinsoo Chung
- Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Kang Hyun Lee
- Center for Prostate Cancer, Hospital, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
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Kormi SMA, Ardehkhani S, Kerachian MA. New insights into colorectal cancer screening and early detection tests. COLORECTAL CANCER 2017. [DOI: 10.2217/crc-2017-0007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Colorectal cancer (CRC) is a common cancer in both men and women worldwide. Creating a diagnostic panel is necessary for early diagnosis which could lead to a better long-term survival in cancer patients. Colonoscopy every 10 years, starting at age 50, is the preferred CRC screening test. Many studies have been worked on potential diagnostic biomarkers of CRC. In this article, we described the recent evolutions in the development of CRC noninvasive screening assays. Recently, a multifunctional fecal DNA test has been available commercially in the USA. A few other US FDA-approved tests like Epi proColon® (Epigenomics AG, Berlin, Germany) are also available now. Although a new marker class for fecal occult blood test, a novel biomarker based on fecal bacteria in CRC patients and circulating tumor cells are under investigation, there is still a strong need to do more research for CRC screening strategies.
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Affiliation(s)
- Seyed Mohammad Amin Kormi
- Cancer Genetics Research Unit, Reza Radiotherapy & Oncology Center, Mashhad, Iran
- Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran
| | - Shima Ardehkhani
- Department of Applied Science & Technology, University of Payame Noor, Tehran, Iran
| | - Mohammad Amin Kerachian
- Cancer Genetics Research Unit, Reza Radiotherapy & Oncology Center, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Genetics, Faculty of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
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41
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Alonso-Alconada L, Barbazan J, Candamio S, Falco JL, Anton C, Martin-Saborido C, Fuster G, Sampedro M, Grande C, Lado R, Sampietro-Colom L, Crego E, Figueiras S, Leon-Mateos L, Lopez-Lopez R, Abal M. PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system. Clin Transl Oncol 2017; 20:630-638. [PMID: 29058262 DOI: 10.1007/s12094-017-1760-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 09/30/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. METHODS PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. RESULTS This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. CONCLUSION The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.
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Affiliation(s)
- L Alonso-Alconada
- Translational Medical Oncology, CIBERONC, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n, 15706, Santiago de Compostela, Spain
| | - J Barbazan
- Translational Medical Oncology, CIBERONC, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n, 15706, Santiago de Compostela, Spain
| | - S Candamio
- Translational Medical Oncology, CIBERONC, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n, 15706, Santiago de Compostela, Spain
| | - J L Falco
- Antares Consulting, Barcelona, Spain
| | - C Anton
- UETeS, Universidad Francisco de Vitoria, Madrid, Spain
| | | | | | - M Sampedro
- Department of Innovation and Transfer, Ramon Dominguez Foundation, Santiago de Compostela, Spain
| | - C Grande
- Medical and Health Technology Innovation Platform (ITEMAS), Galician Network, Santiago de Compostela, Spain
| | - R Lado
- Medical and Health Technology Innovation Platform (ITEMAS), Galician Network, Santiago de Compostela, Spain
| | - L Sampietro-Colom
- Health Technology Assessment Unit, Clinic Hospital, Barcelona, Spain
| | - E Crego
- EFT Consulting, Santiago de Compostela, Spain
| | - S Figueiras
- Health Knowledge Agency (ACIS), Galician Health System (SERGAS), Santiago de Compostela, Spain
| | - L Leon-Mateos
- Health Knowledge Agency (ACIS), Galician Health System (SERGAS), Santiago de Compostela, Spain
| | - R Lopez-Lopez
- Translational Medical Oncology, CIBERONC, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n, 15706, Santiago de Compostela, Spain
| | - M Abal
- Translational Medical Oncology, CIBERONC, Health Research Institute of Santiago (IDIS), University Hospital of Santiago (SERGAS), Trav. Choupana s/n, 15706, Santiago de Compostela, Spain.
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Li S, Chen Q, Li H, Wu Y, Feng J, Yan Y. Mesenchymal circulating tumor cells (CTCs) and OCT4 mRNA expression in CTCs for prognosis prediction in patients with non-small-cell lung cancer. Clin Transl Oncol 2017; 19:1147-1153. [PMID: 28374320 DOI: 10.1007/s12094-017-1652-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 03/20/2017] [Indexed: 12/16/2022]
Abstract
PURPOSE Circulating tumor cells (CTCs) with epithelial-to-mesenchymal transition (EMT) phenotypes might be related to tumor progression while OCT4 expression is involved in tumor metastasis and poor prognosis. But the possible clinical significance of EMT phenotypes of CTCs from non-small-cell lung cancer (NSCLC) patients has still to be demonstrated. Furthermore, none has been investigated the expression of OCT4 in CTCs. We therefore identified the EMT phenotype-based subsets of CTCs and determined the OCT4 expression status of CTCs in NSCLC patients, to explore their possible clinical relevance. METHODS 37 NSCLC patients and ten healthy volunteers were enrolled, respectively. The Canpatrol™ CTC enrichment technique was used to isolate and identify the EMT phenotype-based subsets of CTCs. OCT4 expression in each CTC was also determined. Results were correlated with patients' clinico-pathological features. RESULTS CTCs were detected in 33 of 37 (89.2%) NSCLC patients, and no CTCs were identified in ten healthy volunteers. Three CTCs phenotypes, including epithelial, biophenotypic, and mesenchymal CTCs were identified based on the expression of EMT markers. Mesenchymal CTCs were more commonly found in patients with distant metastasis. Patients with distant metastasis tended to have a higher median CTCs number. OCT4-positive was observed in 21 of 28 (75.0%) patients. High expression of OCT4 tended to occur in advanced patients as well as in distant metastatic patients. CONCLUSIONS The findings suggest that identification of CTCs by EMT markers as well as evaluation of OCT4 expression status by assessment of OCT4 expression in CTCs could serve as potential adjuncts for evaluating metastasis and prognosis in NSCLC patients.
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Affiliation(s)
- S Li
- Department of Cardiothoracic Surgery, Zhujiang Hospital of Southern Medical University, Industrial Road No. 253, Guangzhou, Guangdong, 510280, People's Republic of China
| | - Q Chen
- Department of Cardiothoracic Surgery, Zhujiang Hospital of Southern Medical University, Industrial Road No. 253, Guangzhou, Guangdong, 510280, People's Republic of China
| | - H Li
- Department of Cardiothoracic Surgery, Zhujiang Hospital of Southern Medical University, Industrial Road No. 253, Guangzhou, Guangdong, 510280, People's Republic of China
| | - Y Wu
- Department of Cardiothoracic Surgery, Zhujiang Hospital of Southern Medical University, Industrial Road No. 253, Guangzhou, Guangdong, 510280, People's Republic of China
| | - J Feng
- Department of Cardiothoracic Surgery, Zhujiang Hospital of Southern Medical University, Industrial Road No. 253, Guangzhou, Guangdong, 510280, People's Republic of China
| | - Y Yan
- Department of Cardiothoracic Surgery, Zhujiang Hospital of Southern Medical University, Industrial Road No. 253, Guangzhou, Guangdong, 510280, People's Republic of China.
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Jack RM, Grafton MMG, Rodrigues D, Giraldez MD, Griffith C, Cieslak R, Zeinali M, Kumar Sinha C, Azizi E, Wicha M, Tewari M, Simeone DM, Nagrath S. Ultra-Specific Isolation of Circulating Tumor Cells Enables Rare-Cell RNA Profiling. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2016; 3:1600063. [PMID: 27711257 PMCID: PMC5039969 DOI: 10.1002/advs.201600063] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Indexed: 05/20/2023]
Abstract
The clinical potential of circulating tumor cells (CTCs) in managing cancer metastasis is significant. However, low CTC isolation purities from patient blood have hindered sensitive molecular assays of these rare cells. Described herein is the ultra-pure isolation of CTCs from patient blood samples and how this platform has enabled highly specific molecular (mRNA and miRNA) profiling of patient CTCs.
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Affiliation(s)
- Rhonda M. Jack
- Department of Chemical Engineering3074 H.H. Dow Building2300 Hayward St.Ann ArborMI48109‐2136USA
- Biointerfaces InstituteNorth Campus Research Complex2800 Plymouth Road, Bldg. 90Ann ArborMI48109‐2800USA
| | - Meggie M. G. Grafton
- Department of Chemical Engineering3074 H.H. Dow Building2300 Hayward St.Ann ArborMI48109‐2136USA
- Biointerfaces InstituteNorth Campus Research Complex2800 Plymouth Road, Bldg. 90Ann ArborMI48109‐2800USA
| | - Danika Rodrigues
- Department of Biomedical Engineering1107 Carl A. Gerstacker Building, 2200 Bonisteel, Blvd.Ann ArborMI48109USA
| | - Maria D. Giraldez
- Department of Internal MedicineDivision of Hematology/Oncology and Division of Molecular Medicine and GeneticsUniversity of Michigan109 Zina Pitcher Place, 2061 BSRB ‐ SPC 2200Ann ArborMI48109USA
| | - Catherine Griffith
- Department of Chemical Engineering3074 H.H. Dow Building2300 Hayward St.Ann ArborMI48109‐2136USA
| | - Robert Cieslak
- Department of Chemical Engineering3074 H.H. Dow Building2300 Hayward St.Ann ArborMI48109‐2136USA
| | - Mina Zeinali
- Department of Chemical Engineering3074 H.H. Dow Building2300 Hayward St.Ann ArborMI48109‐2136USA
- Biointerfaces InstituteNorth Campus Research Complex2800 Plymouth Road, Bldg. 90Ann ArborMI48109‐2800USA
- Medical FacultyUniversity of HeidelbergTheodor‐Kutzer‐Ufer1‐3 68167MannheimGermany
| | - Chandan Kumar Sinha
- Michigan Center for Translational PathologyDepartment of PathologyUniversity of Michigan 5309 CCC 5940400 E. Medical Center Dr.Ann ArborMI48109‐0940USA
| | - Ebrahim Azizi
- Comprehensive Cancer CenterUniversity of Michigan Health Systems1500 E. Medical Center DrAnn ArborMI48109USA
| | - Max Wicha
- Comprehensive Cancer CenterUniversity of Michigan Health Systems1500 E. Medical Center DrAnn ArborMI48109USA
| | - Muneesh Tewari
- Biointerfaces InstituteNorth Campus Research Complex2800 Plymouth Road, Bldg. 90Ann ArborMI48109‐2800USA
- Department of Biomedical Engineering1107 Carl A. Gerstacker Building, 2200 Bonisteel, Blvd.Ann ArborMI48109USA
- Department of Internal MedicineDivision of Hematology/Oncology and Division of Molecular Medicine and GeneticsUniversity of Michigan109 Zina Pitcher Place, 2061 BSRB ‐ SPC 2200Ann ArborMI48109USA
- Comprehensive Cancer CenterUniversity of Michigan Health Systems1500 E. Medical Center DrAnn ArborMI48109USA
- Center for Computational Medicine and BioinformaticsUniversity of MichiganRoom 2017, Palmer Commons, 100 Washtenaw AvenueAnn ArborMI48109‐2218USA
| | - Diane M. Simeone
- Department of SurgeryUniversity of Michigan Health Systems1500 E. Medical Center DrAnn ArborMI48109USA
| | - Sunitha Nagrath
- Department of Chemical Engineering3074 H.H. Dow Building2300 Hayward St.Ann ArborMI48109‐2136USA
- Biointerfaces InstituteNorth Campus Research Complex2800 Plymouth Road, Bldg. 90Ann ArborMI48109‐2800USA
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Wu X, Mastronicola R, Tu Q, Faure GC, De Carvalho Bittencourt M, Dolivet G. A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma. BMC Cancer 2016; 16:552. [PMID: 27465596 PMCID: PMC4964083 DOI: 10.1186/s12885-016-2591-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 07/20/2016] [Indexed: 01/04/2023] Open
Abstract
Background Despite aggressive regimens, the clinical outcome of head and neck squamous cell carcinoma remains poor. The detection of circulating tumor cells could potentially improve the management of patients with disseminated cancer, including diagnosis, treatment strategies, and surveillance. Currently, CellSearch® is the most widely used and the only Food and Drug Administration-cleared system for circulating tumor cells detection in patients with metastatic breast, colorectal, or prostate cancer. In most cases of head and neck squamous cell carcinoma, only low counts of circulating tumor cells have been reported. Case presentation A 56-year-old white male with no particular medical history, was diagnosed with a squamous cell carcinoma of oral cavity. According to the imaging results (computed tomography and 18F-fluorodeoxyglucose positron emission tomography / computed tomography) and panendoscopy, the TNM staging was classified as T4N2M0. A non-interruptive pelvimandibulectomy was conducted according to the multidisciplinary meeting advices and the postoperative observations were normal. The patient complained of a painful cervical edema and a trismus 6 weeks after the surgery. A relapse was found by computed tomography and the patient died two weeks later. The search for circulating tumor cells in peripheral venous blood by using the CellSearch® system revealed a very high count compared with published reports at three time points (pre-operative: 400; intra-operative: 150 and post-operative day 7: 1400 circulating tumor cells). Of note, all detected circulating tumor cells were epidermal growth factor receptor negative. Conclusion We report here for the first time a rare case of oral squamous cell carcinoma with extremely high circulating tumor cells counts using the CellSearch® system. The absolute number of circulating tumor cells might predict a particular phase of cancer development as well as a poor survival, potentially contributing to a personalized healthcare.
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Affiliation(s)
- Xianglei Wu
- Laboratory of Immunology, Nancytomique platform, CHRU of Nancy, rue du Morvan, 54500, Vandoeuvre-lès-Nancy, France.,SBS Department, CRAN, UMR 7039 CNRS, University of Lorraine, Avenue de la Forêt de Haye, 54500, Vandoeuvre-lès-Nancy, France.,Department of Otorhinolaryngology - Head and Neck surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, 430071, Wuhan, China
| | - Romina Mastronicola
- SBS Department, CRAN, UMR 7039 CNRS, University of Lorraine, Avenue de la Forêt de Haye, 54500, Vandoeuvre-lès-Nancy, France.,Head and Neck Surgery and Dental Units, Oncologic Surgery Department, Institut de Cancérologie de Lorraine, 6 Avenue de Bourgogne, 54500, Vandœuvre-lès-Nancy, France
| | - Qian Tu
- Laboratory of Immunology, Nancytomique platform, CHRU of Nancy, rue du Morvan, 54500, Vandoeuvre-lès-Nancy, France.,SBS Department, CRAN, UMR 7039 CNRS, University of Lorraine, Avenue de la Forêt de Haye, 54500, Vandoeuvre-lès-Nancy, France
| | - Gilbert Charles Faure
- Laboratory of Immunology, Nancytomique platform, CHRU of Nancy, rue du Morvan, 54500, Vandoeuvre-lès-Nancy, France.,SBS Department, CRAN, UMR 7039 CNRS, University of Lorraine, Avenue de la Forêt de Haye, 54500, Vandoeuvre-lès-Nancy, France
| | - Marcelo De Carvalho Bittencourt
- Laboratory of Immunology, Nancytomique platform, CHRU of Nancy, rue du Morvan, 54500, Vandoeuvre-lès-Nancy, France. .,SBS Department, CRAN, UMR 7039 CNRS, University of Lorraine, Avenue de la Forêt de Haye, 54500, Vandoeuvre-lès-Nancy, France.
| | - Gilles Dolivet
- SBS Department, CRAN, UMR 7039 CNRS, University of Lorraine, Avenue de la Forêt de Haye, 54500, Vandoeuvre-lès-Nancy, France.,Head and Neck Surgery and Dental Units, Oncologic Surgery Department, Institut de Cancérologie de Lorraine, 6 Avenue de Bourgogne, 54500, Vandœuvre-lès-Nancy, France
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Kahlert UD, Mooney SM, Natsumeda M, Steiger HJ, Maciaczyk J. Targeting cancer stem-like cells in glioblastoma and colorectal cancer through metabolic pathways. Int J Cancer 2016; 140:10-22. [PMID: 27389307 DOI: 10.1002/ijc.30259] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Revised: 06/29/2016] [Accepted: 07/04/2016] [Indexed: 12/12/2022]
Abstract
Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC.
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Affiliation(s)
- U D Kahlert
- Department of Neurosurgery, Heinrich-Heine University Medical Center, Düsseldorf, Germany
| | - S M Mooney
- Department of Biology, University of Waterloo, Waterloo, ON, Canada
| | - M Natsumeda
- Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan
| | - H-J Steiger
- Department of Neurosurgery, Heinrich-Heine University Medical Center, Düsseldorf, Germany
| | - J Maciaczyk
- Department of Neurosurgery, Heinrich-Heine University Medical Center, Düsseldorf, Germany
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Gorges TM, Stein A, Quidde J, Hauch S, Röck K, Riethdorf S, Joosse SA, Pantel K. Improved Detection of Circulating Tumor Cells in Metastatic Colorectal Cancer by the Combination of the CellSearch® System and the AdnaTest®. PLoS One 2016; 11:e0155126. [PMID: 27182774 PMCID: PMC4868337 DOI: 10.1371/journal.pone.0155126] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 04/25/2016] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is one of the major causes of cancer-related death and reliable blood-based prognostic biomarkers are urgently needed. The enumeration and molecular characterization of circulating tumor cells (CTCs) has gained increasing interest in clinical practice. CTC detection by CellSearch® has already been correlated to an unfavorable outcome in metastatic CRC. However, the CTC detection rate in mCRC disease is low compared to other tumor entities. Thus, the use of alternative (or supplementary) assays might help to itemize the prognostic use of CTCs as blood-based biomarkers. In this study, blood samples from 47 mCRC patients were screened for CTCs using the FDA-cleared CellSearch® technology and / or the AdnaTest®. 38 samples could be processed in parallel. We demonstrate that a combined analysis of CellSearch® and the AdnaTest® leads to an improved detection of CTCs in our mCRC patient cohort (positivity rate CellSearch® 33%, AdnaTest® 30%, combined 50%). While CTCs detected with the CellSearch® system were significantly associated with progression-free survival (p = 0.046), a significant correlation regarding overall survival could be only seen when both assays were combined (p = 0.013). These findings could help to establish improved tools to detect CTCs as on-treatment biomarkers for clinical routine in future studies.
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Affiliation(s)
- Tobias M. Gorges
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alexander Stein
- Department of Internal Medicine II and Clinic (Oncology Center), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Julia Quidde
- Department of Internal Medicine II and Clinic (Oncology Center), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Katharina Röck
- 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
| | - Klaus Pantel
- Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- * E-mail:
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ANDERGASSEN ULRICH, KÖLBL ALEXANDRAC, MAHNER SVEN, JESCHKE UDO. Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review). Oncol Rep 2016; 35:1905-15. [DOI: 10.3892/or.2016.4608] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 11/15/2015] [Indexed: 11/06/2022] Open
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Brudvik KW, Seeberg LT, Hugenschmidt H, Renolen A, Schirmer CB, Brunborg C, Bjørnbeth BA, Borgen E, Naume B, Waage A, Wiedswang G. Detection of Circulating Tumor Cells at Surgery and at Follow-Up Assessment to Predict Survival After Two-Stage Liver Resection of Colorectal Liver Metastases. Ann Surg Oncol 2015; 22:4029-4037. [DOI: 10.1245/s10434-015-4482-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Li YQ, Chandran BK, Lim CT, Chen X. Rational Design of Materials Interface for Efficient Capture of Circulating Tumor Cells. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2015; 2:1500118. [PMID: 27980914 PMCID: PMC5115340 DOI: 10.1002/advs.201500118] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2015] [Revised: 05/25/2015] [Indexed: 05/11/2023]
Abstract
Originating from primary tumors and penetrating into blood circulation, circulating tumor cells (CTCs) play a vital role in understanding the biology of metastasis and have great potential for early cancer diagnosis, prognosis and personalized therapy. By exploiting the specific biophysical and biochemical properties of CTCs, various material interfaces have been developed for the capture and detection of CTCs from blood. However, due to the extremely low number of CTCs in peripheral blood, there exists a need to improve the efficiency and specificity of the CTC capture and detection. In this regard, a critical review of the numerous reports of advanced platforms for highly efficient and selective capture of CTCs, which have been spurred by recent advances in nanotechnology and microfabrication, is essential. This review gives an overview of unique biophysical and biochemical properties of CTCs, followed by a summary of the key material interfaces recently developed for improved CTC capture and detection, with focus on the use of microfluidics, nanostructured substrates, and miniaturized nuclear magnetic resonance-based systems. Challenges and future perspectives in the design of material interfaces for capture and detection of CTCs in clinical applications are also discussed.
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Affiliation(s)
- Yong-Qiang Li
- School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue SIngapore 639798 Singapore; School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD-X)Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University Suzhou Jiangsu 215123 China
| | - Bevita K Chandran
- School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue SIngapore 639798 Singapore
| | - Chwee Teck Lim
- Department of Biomedical Engineering Mechanobiology Institute Centre for Advanced 2D Materials National University of Singapore 9 Engineering Drive 1 Singapore 117575 Singapore
| | - Xiaodong Chen
- School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue SIngapore 639798 Singapore
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Bragazzi NL, Amicizia D, Panatto D, Tramalloni D, Valle I, Gasparini R. Quartz-Crystal Microbalance (QCM) for Public Health: An Overview of Its Applications. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2015; 101:149-211. [PMID: 26572979 DOI: 10.1016/bs.apcsb.2015.08.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nanobiotechnologies, from the convergence of nanotechnology and molecular biology and postgenomics medicine, play a major role in the field of public health. This overview summarizes the potentiality of piezoelectric sensors, and in particular, of quartz-crystal microbalance (QCM), a physical nanogram-sensitive device. QCM enables the rapid, real time, on-site detection of pathogens with an enormous burden in public health, such as influenza and other respiratory viruses, hepatitis B virus (HBV), and drug-resistant bacteria, among others. Further, it allows to detect food allergens, food-borne pathogens, such as Escherichia coli and Salmonella typhimurium, and food chemical contaminants, as well as water-borne microorganisms and environmental contaminants. Moreover, QCM holds promises in early cancer detection and screening of new antiblastic drugs. Applications for monitoring biohazards, for assuring homeland security, and preventing bioterrorism are also discussed.
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Affiliation(s)
- Nicola Luigi Bragazzi
- Department of Health Sciences (DISSAL), Via Antonio Pastore 1, University of Genoa, Genoa, Italy
| | - Daniela Amicizia
- Department of Health Sciences (DISSAL), Via Antonio Pastore 1, University of Genoa, Genoa, Italy
| | - Donatella Panatto
- Department of Health Sciences (DISSAL), Via Antonio Pastore 1, University of Genoa, Genoa, Italy
| | - Daniela Tramalloni
- Department of Health Sciences (DISSAL), Via Antonio Pastore 1, University of Genoa, Genoa, Italy
| | - Ivana Valle
- SSD "Popolazione a rischio," Health Prevention Department, Local Health Unit ASL3 Genovese, Genoa, Italy
| | - Roberto Gasparini
- Department of Health Sciences (DISSAL), Via Antonio Pastore 1, University of Genoa, Genoa, Italy.
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