|
1
|
Chen M, Gao L. Carcinoid syndrome presenting as diffuse violaceous cutaneous flushing. Br J Dermatol 2025; 192:772-773. [PMID: 39460433 DOI: 10.1093/bjd/ljae424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/23/2024] [Accepted: 10/23/2024] [Indexed: 10/28/2024]
Abstract
We report a rare case of carcinoid syndrome presenting as deep red to violaceous erythema and diarrhoea. Early diagnosis and treatment by multidisciplinary team is crucial in improving prognosis and outcomes.
Collapse
Affiliation(s)
- Meiqing Chen
- Department of Dermatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, China
- Xiamen Clinical Research Center for Cancer Therapy, Xiamen, Fujian, China
| | - Lujuan Gao
- Department of Dermatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, China
- Xiamen Clinical Research Center for Cancer Therapy, Xiamen, Fujian, China
- Department of Dermatology, Zhongshan Hospital Fudan University, Shanghai,China
| |
Collapse
|
|
2
|
Cheng Y, Zhang P, Lu M, Chen Z, Song L, Shi S, Ye F, Zhang X, Liu B, Ji D, Zhang Y, Su W, Shi M, Fan S, Tan P, Zhong C. Efficacy and safety of surufatinib plus toripalimab in treatment-naive, PD-L1-positive, advanced or metastatic non-small-cell lung cancer and previously treated small-cell lung cancer: an open-label, single-arm, multicenter, multi-cohort phase II trial. Cancer Immunol Immunother 2025; 74:83. [PMID: 39891720 PMCID: PMC11787074 DOI: 10.1007/s00262-024-03932-x] [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: 07/03/2024] [Accepted: 12/26/2024] [Indexed: 02/03/2025]
Abstract
BACKGROUND Combining the programmed death-1 inhibitor toripalimab and the angio-immuno kinase inhibitor surufatinib showed preliminary antitumor activity in patients with advanced solid tumors in a phase I study. Here, we report the efficacy and safety of this combination regimen in treatment-naive advanced or metastatic non-small-cell lung cancer (NSCLC) patients with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or greater (PD-L1-positive) and patients with previously treated small-cell lung cancer (SCLC). METHODS This open-label, single-arm phase II study included patients with treatment-naive advanced or metastatic PD-L1-positive NSCLC or previously treated SCLC in China. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS Forty-three patients were treated (NSCLC cohort, n = 23; SCLC cohort, n = 20). ORRs (95% CIs) were 57.1% (34.0-78.2) in the NSCLC cohort and 15.8% (3.4-39.6) in the SCLC cohort. Median duration of response was not reached (NR) in both cohorts. Median PFS was 9.6 (5.5-NR) and 3.0 months (2.8-4.1), respectively, and median OS was 24.3 (10.8-NR) and 11.0 months (5.0-15.7), respectively. Grade ≥ 3 treatment-related adverse events were reported in 24 patients (55.8%) overall. CONCLUSION Surufatinib plus toripalimab showed encouraging antitumor activity and a tolerable safety profile in patients with treatment-naive advanced or metastatic PD-L1-positive NSCLC and previously treated SCLC.
Collapse
MESH Headings
- Humans
- Male
- Female
- Lung Neoplasms/drug therapy
- Lung Neoplasms/pathology
- Lung Neoplasms/metabolism
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/metabolism
- Middle Aged
- Aged
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/adverse effects
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Small Cell Lung Carcinoma/drug therapy
- Small Cell Lung Carcinoma/pathology
- Small Cell Lung Carcinoma/metabolism
- B7-H1 Antigen/metabolism
- B7-H1 Antigen/antagonists & inhibitors
- Adult
- Oxazoles/therapeutic use
- Oxazoles/administration & dosage
- Aged, 80 and over
- Cohort Studies
Collapse
Affiliation(s)
- Ying Cheng
- Department of Oncology, Jilin Cancer Hospital, 1066 Jinhu Rd, High-Tech Zone, Changchun, China.
| | - Panpan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China
| | - Ming Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, No.52 Fucheng Road, Haidian District, Beijing, China
| | - Zhendong Chen
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, Anhui, China
| | - Lijie Song
- First Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 East Jianshe Road, Erqi District, Zhengzhou, Henan, China
| | - Si Shi
- Department of Pancreatic Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, No.270 Dong'an Road, Xuhui District, Shanghai, China
| | - Feng Ye
- Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Siming District, Xiamen, Fujian, China
| | - Xing Zhang
- Biotherapy Center, Sun Yat-Sen University Cancer Center, No.651 East Dongfeng Road, Yuexiu District, Guangzhou, Guangdong, China
| | - Baorui Liu
- The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, No.321 Zhongshan Road, Nanjing, Jiangsu, China
| | - Dongmei Ji
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, No.270 Dong'an Road, Xuhui District, Shanghai, China
| | - Yanqiao Zhang
- Second Department of Gastroenterology, Harbin Medical University Cancer Hospital, No.150 Haping Road, Nangang District, Harbin, Heilongjiang, China
| | - Weiguo Su
- HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Michael Shi
- HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Songhua Fan
- HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Panfeng Tan
- HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Chen Zhong
- HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| |
Collapse
|
|
3
|
Jian L, Wang Y, Hao Y, Zhao D, Songlin W, Qun Q, Daojiang L. Development of Pseudosacral Cyst Following Surgery for Primary Presacral Neuroendocrine Tumors With Liver Metastasis: A Case Report. Clin Case Rep 2024; 12:e9672. [PMID: 39629039 PMCID: PMC11612513 DOI: 10.1002/ccr3.9672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/19/2024] [Accepted: 11/04/2024] [Indexed: 12/06/2024] Open
Abstract
Presacral neuroendocrine tumor (PSNET) is a rare disease that currently lacks a standardized treatment approach. In this report, we present a unique case of PSNET with liver metastasis that progressed into a pseudosacral cyst following complete surgical resection and sulfatinib treatment with radiofrequency ablation. Before undergoing surgical treatment for presacral neuroendocrinology, it is important to consider the potential risks of poor healing of the presacral incision and formation of pseudocysts. These complications may be caused by various factors, including the procedure itself and the use of targeted drugs.
Collapse
Affiliation(s)
- Li Jian
- Department of Colorectal and Anal SurgeryZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Clinical Center of Intestinal and Colorectal Diseases of Hubei ProvinceHubeiChina
- Hubei Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei ProvinceHubeiChina
| | - Youheng Wang
- Department of Colorectal and Anal SurgeryZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Clinical Center of Intestinal and Colorectal Diseases of Hubei ProvinceHubeiChina
- Hubei Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei ProvinceHubeiChina
| | - Yu Hao
- Department of RadiologyZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
| | - Ding Zhao
- Department of Colorectal and Anal SurgeryZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Clinical Center of Intestinal and Colorectal Diseases of Hubei ProvinceHubeiChina
- Hubei Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei ProvinceHubeiChina
| | - Wan Songlin
- Department of Colorectal and Anal SurgeryZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Clinical Center of Intestinal and Colorectal Diseases of Hubei ProvinceHubeiChina
- Hubei Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei ProvinceHubeiChina
| | - Qian Qun
- Department of Colorectal and Anal SurgeryZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Clinical Center of Intestinal and Colorectal Diseases of Hubei ProvinceHubeiChina
- Hubei Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei ProvinceHubeiChina
| | - Li Daojiang
- Department of Colorectal and Anal SurgeryZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Clinical Center of Intestinal and Colorectal Diseases of Hubei ProvinceHubeiChina
- Hubei Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityWuhanHubeiChina
- Quality Control Center of Colorectal and Anal Surgery of Health Commission of Hubei ProvinceHubeiChina
| |
Collapse
|
|
4
|
Liu Y, Yang X, Wang Y, Xie S, Li M, You J, Tang Y, Zhao J, Weng D. Efficacy and safety of surufatinib in the treatment of patients with neuroendocrine tumor: a real-world study in Chinese population. BMC Cancer 2024; 24:1342. [PMID: 39482595 PMCID: PMC11529162 DOI: 10.1186/s12885-024-13089-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 10/23/2024] [Indexed: 11/03/2024] Open
Abstract
BACKGROUND Neuroendocrine tumors (NETs) are rare neoplasms that originate from peptidergic neurons and neuroendocrine cells. Due to their increasing incidence, effective treatment strategies are required. Surufatinib, a novel small-molecule inhibitor with antiangiogenic and immunomodulatory effects, has shown promise in clinical trials for advanced NETs. However, the efficacy and safety of surufatinib are influenced by multiple factors, and there is currently a lack of sufficient real-world studies to explore these potential influencing factors. METHODS We conducted a retrospective study on 133 patients with NETs who were treated with surufatinib at Sun Yat-sen University Cancer Center. Patients were histologically confirmed to have primary NETs. Statistical analyses, including Cox regression models and Kaplan-Meier curves, were conducted to assess the impact of the primary tumor site on progression-free survival (PFS) and overall survival (OS). RESULTS Patients with gastroenteropancreatic NETs (GEP-NETs) exhibited significantly longer PFS and OS compared to extraGEP-NETs patients. Subgroup analyses also revealed variations in survival outcomes among patients with liver metastases depending on the primary tumor site. Adverse events (AEs), including proteinuria and increased bilirubin, were more common in GEP-NETs patients. These findings emphasize the importance of considering primary tumor site in treatment decisions for NETs. CONCLUSIONS Primary tumor site is a critical factor influencing the efficacy of surufatinib in NETs. Clinicians should consider this factor when determining treatment strategies.
Collapse
Affiliation(s)
- Yuanyuan Liu
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xinyi Yang
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yan Wang
- Department of Medical Oncology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou, China
| | - Songzuo Xie
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Minxing Li
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jinqi You
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yan Tang
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Jingjing Zhao
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Desheng Weng
- Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
| |
Collapse
|
|
5
|
Tomuleasa C, Tigu AB, Munteanu R, Moldovan CS, Kegyes D, Onaciu A, Gulei D, Ghiaur G, Einsele H, Croce CM. Therapeutic advances of targeting receptor tyrosine kinases in cancer. Signal Transduct Target Ther 2024; 9:201. [PMID: 39138146 PMCID: PMC11323831 DOI: 10.1038/s41392-024-01899-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 05/29/2024] [Accepted: 06/14/2024] [Indexed: 08/15/2024] Open
Abstract
Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.
Collapse
Affiliation(s)
- Ciprian Tomuleasa
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
- Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj Napoca, Romania.
- Academy of Romanian Scientists, Ilfov 3, 050044, Bucharest, Romania.
| | - Adrian-Bogdan Tigu
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Academy of Romanian Scientists, Ilfov 3, 050044, Bucharest, Romania
| | - Raluca Munteanu
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
- Academy of Romanian Scientists, Ilfov 3, 050044, Bucharest, Romania
| | - Cristian-Silviu Moldovan
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - David Kegyes
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
- Academy of Romanian Scientists, Ilfov 3, 050044, Bucharest, Romania
| | - Anca Onaciu
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Diana Gulei
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Gabriel Ghiaur
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
- Department of Leukemia, Sidney Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Hermann Einsele
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania
- Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany
| | - Carlo M Croce
- Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
| |
Collapse
|
|
6
|
Sebastian A, Abu Rabah RR, Zaraei SO, Vunnam S, Sultan S, Anbar HS, El-Gamal R, Tarazi H, Sarg N, Alhamad DW, Al Shamma SA, Shahin AI, Omar HA, Al-Tel TH, El-Gamal MI. Design, synthesis, biological evaluation, and in silico studies of novel pyridopyridine derivatives as anticancer candidates targeting FMS kinase. Eur J Med Chem 2024; 274:116557. [PMID: 38850857 DOI: 10.1016/j.ejmech.2024.116557] [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: 04/29/2024] [Revised: 05/29/2024] [Accepted: 05/30/2024] [Indexed: 06/10/2024]
Abstract
Design and synthesis of novel 4-carboxamidopyrido[3,2-b]pyridine derivatives as novel rigid analogues of sorafenib are reported herein. The target compounds showed potent antiproliferative activities against a panel of NCI-60 cancer cell lines as well as hepatocellular carcinoma cell line. Compounds 8g and 9f were among the most promising derivatives in terms of effectiveness and safety. Therefore, they were further examined to demonstrate their ability to induce apoptosis and alter cell cycle progression in hepatocellular carcinoma cells. The most potent compounds were tested against a panel of kinases that indicated their selectivity against FMS kinase. Compounds 8g and 8h showed the most potent activities against FMS kinase with IC50 values of 21.5 and 73.9 nM, respectively. The two compounds were also tested in NanoBRET assay to investigate their ability to inhibit FMS kinase in cells (IC50 = 563 nM (8g) and 1347 nM (8h) vs. IC50 = 1654 nM for sorafenib). Furthermore, compounds 8g and 8h possess potent inhibitory activities against macrophages when investigated in bone marrow-derived macrophages (BMDM) assay (IC50 = 56 nM and 167 nM, respectively, 164 nM for sorafenib). The safety and selectivity of these compounds were confirmed when tested against normal cell lines. Their safety profile was further confirmed using hERG assay. In silico studies were carried out to investigate their binding modes in the active site of FMS kinase, and to develop a QSAR model for these new motifs.
Collapse
Affiliation(s)
- Anusha Sebastian
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Reinad R Abu Rabah
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Seyed-Omar Zaraei
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Srinivasulu Vunnam
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Shaista Sultan
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Hanan S Anbar
- Department of Pharmaceutical Sciences, Dubai Pharmacy College for Girls, Dubai, 19099, United Arab Emirates
| | - Randa El-Gamal
- Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt
| | - Hamadeh Tarazi
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Nadin Sarg
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Dima W Alhamad
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Salma A Al Shamma
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Afnan I Shahin
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Hany A Omar
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt
| | - Taleb H Al-Tel
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates.
| | - Mohammed I El-Gamal
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
| |
Collapse
|
|
7
|
Leng Q, Lv W, Yang H, Li X, Wang W, Cheng K, Chang C, Cao D. Case report: Remarkable response to later-line surufatinib in an adult patient with liver metastatic of pancreatoblastoma. Front Pharmacol 2024; 15:1361628. [PMID: 38948477 PMCID: PMC11211453 DOI: 10.3389/fphar.2024.1361628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 05/24/2024] [Indexed: 07/02/2024] Open
Abstract
Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of β-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.
Collapse
Affiliation(s)
- Qingqing Leng
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wanrui Lv
- Department of Oncology, Meishan Municipal People’s Hospital, Meishan, Sichuan, China
| | - Heqi Yang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaofen Li
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Weiya Wang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ke Cheng
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chen Chang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dan Cao
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
|
8
|
Zhang P, Shi S, Xu J, Chen Z, Song L, Zhang X, Cheng Y, Zhang Y, Ye F, Li Z, Yin F, Ji D, Gao H, Li Y, Chen W, Yang M, Weng D, Wu C, Ma Y, Sheng W, Zhao Y, Yin X, Shen W, Su W, Shi M, Fan S, Tan P, Xu Q, Lu M, Shen L. Surufatinib plus toripalimab in patients with advanced neuroendocrine tumours and neuroendocrine carcinomas: An open-label, single-arm, multi-cohort phase II trial. Eur J Cancer 2024; 199:113539. [PMID: 38237373 DOI: 10.1016/j.ejca.2024.113539] [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: 11/09/2023] [Revised: 12/29/2023] [Accepted: 01/05/2024] [Indexed: 02/13/2024]
Abstract
BACKGROUND The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib revealed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumours in a phase I study. PATIENTS AND METHODS This was an open-label, single-arm, multi-cohort phase II study in China. Patients with advanced neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs) or mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) who had failed or were intolerable of standard treatment were given surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary end-point was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end-points included duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS Forty patients were enrolled into two cohorts by tumour types (NET, n = 19; NEC-MiNEN, n = 21). ORRs (95% CIs) were 21.1% (6.1-45.6) and 23.8% (8.2-47.2) in the NET and NEC-MiNEN cohorts, respectively. Median DoR was 7.1 months (6.9-not evaluable [NE]) and 4.1 months (3.0-NE), respectively. Median PFS was 9.6 months (4.1-NE) and 4.1 months (1.5-5.5); median OS was 27.3 (15.3-NE) and 10.9 months (9.1-14.6), respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 18 (45.0%) patients. CONCLUSIONS Surufatinib plus toripalimab showed antitumour activity and a tolerable safety profile in patients with previously treated NETs/NECs/MiNENs. Further study of this combination regimen is ongoing for advanced NECs, for which current therapeutic options remain limited. CLINICALTRIALS gov: NCT04169672.
Collapse
Affiliation(s)
- Panpan Zhang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Si Shi
- Department of Pancreatic Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, No.270 Dong'an Road, Xuhui district, Shanghai, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center of Chinese PLA General Hospital, No.8 East Avenue, Fengtai District, Beijing, China
| | - Zhendong Chen
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, Anhui, China
| | - Lijie Song
- First Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 East Jianshe Road, Erqi District, Zhengzhou, Henan, China
| | - Xing Zhang
- Biotherapy Center, Sun Yat-sen University Cancer Center, No.651 East Dongfeng Road, Yuexiu District, Guangzhou, Guangdong, China
| | - Ying Cheng
- Department of Thoracic Oncology, Jilin Cancer Hospital, No.1066 Jinghu Avenue, Gaoxin District, Changchun, Jilin,China
| | - Yanqiao Zhang
- Second Department of Gastroenterology, Harbin Medical University Cancer Hospital, No.150 Haping Road, Nangang District, Harbin, Heilongjiang, China
| | - Feng Ye
- Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Siming District, Xiamen, Fujian, China
| | - Zhiping Li
- Department of Abdominal Oncology, West China Hospital of Sichuan University, No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China
| | - Fei Yin
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, No.12 Jiankan Road, Shijiazhuang, Hebei, China
| | - Dongmei Ji
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, No.270 Dong'an Road, Xuhui district, Shanghai, China
| | - Heli Gao
- Department of Pancreatic Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, No.270 Dong'an Road, Xuhui district, Shanghai, China
| | - Yi Li
- Department of Gastrointestinal Oncology, The Fifth Medical Center of Chinese PLA General Hospital, No.8 East Avenue, Fengtai District, Beijing, China
| | - Wei Chen
- Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Economic and Technological Development Zone, Hefei, Anhui, China
| | - Minjie Yang
- First Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 East Jianshe Road, Erqi District, Zhengzhou, Henan, China
| | - Desheng Weng
- Biotherapy Center, Sun Yat-sen University Cancer Center, No.651 East Dongfeng Road, Yuexiu District, Guangzhou, Guangdong, China
| | - Chunjiao Wu
- Phase I Study Ward, Jilin Cancer Hospital, No.1066 Jinghu Avenue, Gaoxin District, Changchun, Jilin, China
| | - Yue Ma
- Second Department of Gastroenterology, Harbin Medical University Cancer Hospital, No.150 Haping Road, Nangang District, Harbin, Heilongjiang, China
| | - Wang Sheng
- Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Siming District, Xiamen, Fujian, China
| | - Yaqin Zhao
- Department of Abdominal Oncology, West China Hospital of Sichuan University, No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China
| | - Xiaolei Yin
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, No.12 Jiankan Road, Shijiazhuang, Hebei, China
| | - Weina Shen
- Phase I Study Ward, Fudan University Shanghai Cancer Center, No.270 Dong'an Road, Xuhui district, Shanghai, China
| | - Weiguo Su
- HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Michael Shi
- Clinical & Regulatory Department, HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Songhua Fan
- Clinical & Regulatory Department, HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Panfeng Tan
- Clinical & Regulatory Department, HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Qian Xu
- Clinical & Regulatory Department, HUTCHMED Limited, Building 4, 720 Cailun Road, Pilot Free Trade Zone, Shanghai, China
| | - Ming Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
| |
Collapse
|
|
9
|
Szczepanski JM, Rudolf MA, Shi J. Clinical Evaluation of the Pancreatic Cancer Microenvironment: Opportunities and Challenges. Cancers (Basel) 2024; 16:794. [PMID: 38398185 PMCID: PMC10887250 DOI: 10.3390/cancers16040794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/10/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Advances in our understanding of pancreatic ductal adenocarcinoma (PDAC) and its tumor microenvironment (TME) have the potential to transform treatment for the hundreds of thousands of patients who are diagnosed each year. Whereas the clinical assessment of cancer cell genetics has grown increasingly sophisticated and personalized, current protocols to evaluate the TME have lagged, despite evidence that the TME can be heterogeneous within and between patients. Here, we outline current protocols for PDAC diagnosis and management, review novel biomarkers, and highlight potential opportunities and challenges when evaluating the PDAC TME as we prepare to translate emerging TME-directed therapies to the clinic.
Collapse
Affiliation(s)
| | | | - Jiaqi Shi
- Department of Pathology and Clinical Labs, University of Michigan, Ann Arbor, MI 48109, USA; (J.M.S.); (M.A.R.)
| |
Collapse
|
|
10
|
Alkubaisi BO, Aljobowry R, Ali SM, Sultan S, Zaraei SO, Ravi A, Al-Tel TH, El-Gamal MI. The latest perspectives of small molecules FMS kinase inhibitors. Eur J Med Chem 2023; 261:115796. [PMID: 37708796 DOI: 10.1016/j.ejmech.2023.115796] [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: 07/03/2023] [Revised: 09/03/2023] [Accepted: 09/04/2023] [Indexed: 09/16/2023]
Abstract
FMS kinase is a type III tyrosine kinase receptor that plays a central role in the pathophysiology and management of several diseases, including a range of cancer types, inflammatory disorders, neurodegenerative disorders, and bone disorders among others. In this review, the pathophysiological pathways of FMS kinase in different diseases and the recent developments of its monoclonal antibodies and inhibitors during the last five years are discussed. The biological and biochemical features of these inhibitors, including binding interactions, structure-activity relationships (SAR), selectivity, and potencies are discussed. The focus of this article is on the compounds that are promising leads and undergoing advanced clinical investigations, as well as on those that received FDA approval. In this article, we attempt to classify the reviewed FMS inhibitors according to their core chemical structure including pyridine, pyrrolopyridine, pyrazolopyridine, quinoline, and pyrimidine derivatives.
Collapse
Affiliation(s)
- Bilal O Alkubaisi
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Raya Aljobowry
- College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Salma M Ali
- College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Sara Sultan
- College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Seyed-Omar Zaraei
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Anil Ravi
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates
| | - Taleb H Al-Tel
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates.
| | - Mohammed I El-Gamal
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
| |
Collapse
|
|
11
|
Al-Toubah T, Strosberg J, Hallanger-Johnson J, El-Haddad G. Targeted radionuclide therapy in endocrine-related cancers: advances in the last decade. Front Endocrinol (Lausanne) 2023; 14:1187870. [PMID: 38053729 PMCID: PMC10694449 DOI: 10.3389/fendo.2023.1187870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 10/26/2023] [Indexed: 12/07/2023] Open
Abstract
Targeted radionuclide therapy plays an increasingly important role in managing endocrine-related tumors and significantly advances the therapeutic landscape for patients with these diseases. With increasing FDA-approved therapies and advances in the field, come an increased knowledge of the potential for long-term toxicities associated with these therapies and the field must develop new strategies to increase potency and efficacy while individualizing the selection of patients to those most likely to respond to treatment. Novel agents and modalities of therapy are also being explored. This review will discuss the current landscape and describe the avenues for growth in the field currently being explored.
Collapse
Affiliation(s)
- Taymeyah Al-Toubah
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| | - Jonathan Strosberg
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| | - Julie Hallanger-Johnson
- Department of Head and Neck - Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| | - Ghassan El-Haddad
- Department of Radiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
- Department of Nuclear Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
| |
Collapse
|
|
12
|
Guo M, Hu S, Xiao Y, Cao Z, Huang Z, Liu Y, An X, Zhang G, Zheng X. Visual analysis of lung neuroendocrine tumors based on CiteSpace knowledge graph. Front Endocrinol (Lausanne) 2023; 14:1214404. [PMID: 37745715 PMCID: PMC10516576 DOI: 10.3389/fendo.2023.1214404] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 08/16/2023] [Indexed: 09/26/2023] Open
Abstract
Objective The relevant literatures in the field of pulmonary neuroendocrine tumor were analyzed to understand the lineage, hot spots and development trends of research in this tumor. Method The Web of Science core collection was searched for English-language literature about neuroendocrine tumors of the lung published between 2000 and 2022. CiteSpace software was imported for visualization analysis of countries, institutions, co-cited authors and co-cited journals and sorting of high-frequency keywords, as well as co-cited references and keyword co-occurrence, clustering and bursting display. Results A total of 594 publications on neuroendocrine tumours of the lung were available, from 2000 to 2022, with an overall upward trend of annual publications in the literature. Authors or institutions from the United States, Italy, Japan and China were more active in this field, but there was little cooperation among the major countries. Co-cited references and keyword co-occurrence and cluster analysis showed that research on diagnostic instruments, pathogenesis, ectopic ACTH signs, staging and prognosis and treatment was a current research hotspot. The keyword bursts suggested that therapeutic approaches might be a key focus of future research into the field for pulmonary neuroendocrine tumors. Conclusion Over these 20 years, research related to neuroendocrine tumors of the lung has increased in fervour, with research on diagnostic instruments, pathogenesis, ectopic ACTH signs, staging and prognosis, and treatment being the main focus of research. Therapeutic treatments may be the future research trend in this field.
Collapse
Affiliation(s)
- Mingjie Guo
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Shaowen Hu
- Department of Clinical Medicine, Medical School of Henan University, Kaifeng, China
| | - Yaifei Xiao
- Department of Clinical Medicine, Medical School of Henan University, Kaifeng, China
| | - Zhan Cao
- Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhichao Huang
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Yalong Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Xiaokang An
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Guoyu Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Xianjie Zheng
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China
| |
Collapse
|
|
13
|
Mosalem O, Sonbol MB, Halfdanarson TR, Starr JS. Tyrosine Kinase Inhibitors and Immunotherapy Updates in Neuroendocrine Neoplasms. Best Pract Res Clin Endocrinol Metab 2023; 37:101796. [PMID: 37414652 DOI: 10.1016/j.beem.2023.101796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/08/2023]
Abstract
Neuroendocrine tumors (NETs) represent a heterogeneous group of malignancies that arise from neuroendocrine cells dispersed throughout the organs/tissues of the body. Treatment of advanced/metastatic disease varies depending on tumor origin and grade. Somatostatin analogs (SSA) have been the mainstay first-line treatment in the advanced/metastatic setting for tumor control and managing hormonal syndromes. Treatments beyond SSAs have expanded to include everolimus (mTOR inhibitor), tyrosine kinase inhibitors (TKI) (e.g., sunitinib), and peptide receptor radionuclide therapy (PRRT) with the choice of therapy to some extent dictated by the anatomic origin of the NETs. This review will focus on emerging systemic treatments for advanced/metastatic NETs, particularly TKIs, and immunotherapy.
Collapse
Affiliation(s)
- Osama Mosalem
- Division of Hematology and Oncology, Mayo Clinic Cancer Center, Jacksonville, FL, USA.
| | | | | | - Jason S Starr
- Division of Hematology and Oncology, Mayo Clinic Cancer Center, Jacksonville, FL, USA.
| |
Collapse
|
|
14
|
Malladi UD, Chimata SK, Bhashyakarla RK, Lingampally SR, Venkannagari VR, Mohammed ZA, Vargiya RV. Duodenal neuroendocrine tumor-tertiary care centre experience: A case report. World J Transl Med 2023; 11:1-8. [DOI: 10.5528/wjtm.v11.i1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/05/2023] [Accepted: 08/17/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms arising from neuroendocrine cells, which contribute a small fraction of gastrointestinal malignancies. Duodenal neuroendocrine tumors (dNETs) represent 2% of all gastroenteropancreatic NENs. NENs are heterogeneous in terms of clinical symptoms, location, and prognosis. Non-functional NETs are mostly asymptomatic and need a high degree of clinical suspicion. Diagnosis of NETs is by endoscopic, endosonographic biopsy, and histopathological examination with immunohistochemistry staining for synaptophysin and chromogranin A.
CASE SUMMARY We present case reports of 5 patients obtained over a period of 10 years in our center with dNETs. One patient had moderately differentiated NET and the remaining four had well-differentiated NET. Surveillance endoscopy was recommended in all the patients and is kept under regular follow-up after performing endoscopic therapy using endoscopic mucosal resection in 4 of them and one patient was advised to undergo a Whipple procedure.
CONCLUSION Recently, the number of reported cases of NETs has increased due to advancements in diagnostic modalities and prevalence because of longer survival duration. The management differs based on the site, size, proliferation grade, and locally invasive pattern. They are slow-growing tumors with a good overall prognosis. The prognosis correlates with local lymph node status and metastasis.
Collapse
Affiliation(s)
- Uma Devi Malladi
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Suraj Kumar Chimata
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Ramesh Kumar Bhashyakarla
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Sahitya Reddy Lingampally
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Vikas Reddy Venkannagari
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Zeeshan Ali Mohammed
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Rahul Vijay Vargiya
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| |
Collapse
|
|
15
|
Tang Y, Chen X, Lu X, Yuan Z, Yang Y, Qiu C, Li H. Case Report: Primary hepatic neuroendocrine tumor: two cases report with literature review. Front Oncol 2023; 13:1225583. [PMID: 37601674 PMCID: PMC10436565 DOI: 10.3389/fonc.2023.1225583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 07/20/2023] [Indexed: 08/22/2023] Open
Abstract
Background & Aims Primary hepatic neuroendocrine tumors (PHNETs) are rare malignant liver tumors that present diagnostic challenges owing to their rarity and absence of specific clinical features. This study aimed to investigate the characteristics of this rare liver tumor to enhance our understanding of the disease, improve diagnostic accuracy, and explore standardized diagnostic and treatment approaches. Case description During physical examination, two elderly women, aged 64 and 74 years, were found to have liver masses. 18F-FDG Positron Emission Tomography-Computed Tomography (18F-FDG PET-CT) and Ga68-DOTATATE PET-CT scans of both individuals revealed multiple liver masses that were initially suspected to be hepatic neuroendocrine tumors. Subsequent puncture pathology confirmed the diagnosis of neuroendocrine tumors. Furthermore, in Case 1, the tumor was also detected by 18F-FDG PET-CT in the lung, suggesting a metastatic tumor, in conjunction with liver immunohistochemistry and imaging findings. Laboratory tests revealed no significant abnormalities in liver function or autoimmune liver disease indicators, and there was no evidence of viral hepatitis infection. However, partial hepatectomy was not indicated for cases with distant metastasis or multiple space-occupying lesions. Individualized treatment approaches have been developed for such situations. A large portion of the tumor underwent Transarterial Embolization (TAE), and targeted combination chemotherapy or endocrine therapy was administered based on the pathological results. During regular follow-ups a 13 and 12 months, the tumor remained stable. The patients' quality of life was good, and their psychological well-being was healthy. They led active lifestyles, demonstrated a thorough understanding of their disease and its progression, and actively cooperated during the follow-up process. Conclusion Our findings suggest that a combination of serological, radiological, and immunohistochemical examinations can aid in the diagnosis of PHNET. In addition, we determined that TAE combined with drug therapy could be an effective method for controlling PHNET progression. Regular postoperative follow-ups are important for monitoring the prognosis and tumor progression status of patients with PHNET.
Collapse
Affiliation(s)
- Yongsheng Tang
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xianyu Chen
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xu Lu
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zenan Yuan
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yang Yang
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chunhui Qiu
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hua Li
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
16
|
Roskoski R. Small molecule protein kinase inhibitors approved by regulatory agencies outside of the United States. Pharmacol Res 2023; 194:106847. [PMID: 37454916 DOI: 10.1016/j.phrs.2023.106847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 07/03/2023] [Indexed: 07/18/2023]
Abstract
Owing to genetic alterations and overexpression, the dysregulation of protein kinases plays a significant role in the pathogenesis of many autoimmune and neoplastic disorders and protein kinase antagonists have become an important drug target. Although the efficacy of imatinib in the treatment of chronic myelogenous leukemia in the United States in 2001 was the main driver of protein kinase inhibitor drug discovery, this was preceded by the approval of fasudil (a ROCK antagonist) in Japan in 1995 for the treatment of cerebral vasospasm. There are 21 small molecule protein kinase inhibitors that are approved in China, Japan, Europe, and South Korea that are not approved in the United Sates and 75 FDA-approved inhibitors in the United States. Of the 21 agents, eleven target receptor protein-tyrosine kinases, eight inhibit nonreceptor protein-tyrosine kinases, and two block protein-serine/threonine kinases. All 21 drugs are orally bioavailable or topically effective. Of the non-FDA approved drugs, sixteen are prescribed for the treatment of neoplastic diseases, three are directed toward inflammatory disorders, one is used for glaucoma, and fasudil is used in the management of vasospasm. The leading targets of kinase inhibitors approved by both international regulatory agencies and by the FDA are members of the EGFR family, the VEGFR family, and the JAK family. One-third of the 21 internationally approved drugs are not compliant with Lipinski's rule of five for orally bioavailable drugs. The rule of five relies on four parameters including molecular weight, number of hydrogen bond donors and acceptors, and the Log of the partition coefficient.
Collapse
Affiliation(s)
- Robert Roskoski
- Blue Ridge Institute for Medical Research, 221 Haywood Knolls Drive, Hendersonville, NC 28791-8717, United States.
| |
Collapse
|
|
17
|
Cai T, Cheng Y, Du Y, Tan P, Li T, Chen Y, Gao L, Fu W. Efficacy and safety of surufatinib in the treatment of advanced solid tumors: a systematic evaluation and meta‑analysis. Oncol Lett 2023; 25:273. [PMID: 37216159 PMCID: PMC10193379 DOI: 10.3892/ol.2023.13859] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 04/17/2023] [Indexed: 05/24/2023] Open
Abstract
Previous retrospective studies have suggested that surufatinib is effective for treating advanced solid tumors; however, the efficacy and safety of this drug needs to be investigated further via high-quality evidence or randomized controlled trials. In the present study, a meta-analysis was carried out to evaluate the safety and effectiveness of surufatinib for patients with advanced solid tumors. Systematic, electronic literature searches were conducted using PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov. The disease control rate (DCR) of surufatinib in solid tumors was 86% [effect size (ES), 0.86; 95% confidence interval (CI), 0.82-0.90; I2=34%; P=0.208] and the objective response rate was 16% (ES, 0.16; 95% CI, 0.12-0.21; I2=48%; P=0.103), while the progressive disease rate was only 9% (ES, 0.09; 95% CI, 0.05-0.15; I2=68%, P=0.014). Surufatinib showed different degrees of adverse reactions during the treatment of solid tumors. Among these adverse events, the incidence of increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 24% (ES, 0.24; 95% CI, 0.18-0.30; I2=45.1%; P=0.141) and 33% (ES, 0.33; 95%CI, 0.28-0.38; I2=63.9%; P=0.040), respectively. In the placebo-controlled trial, the relative risks (RRs) of elevated AST and ALT were 1.04 (95% CI, 0.54-2.02; I2=73.3%; P=0.053) and 0.84 (95% CI, 0.57-1.23; I2=0%; P=0.886), respectively. Overall, surufatinib was characterized by a high DCR and a low disease progression rate, thus indicating that it could exert a good therapeutic effect on solid tumors. Additionally, surufatinib showed a lower RR for adverse effects compared with other treatment modalities.
Collapse
Affiliation(s)
- Tianying Cai
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Yonglang Cheng
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Yichao Du
- Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Peng Tan
- Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Tongxi Li
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Yifan Chen
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Lin Gao
- Department of Health Management, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Wenguang Fu
- Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
- Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| |
Collapse
|
|
18
|
Gül-Klein S, Arnold A, Oberender C, Kuzinska MZ, Alberto Vilchez ME, Mogl MT, Rau B. Appendixneoplasien. COLOPROCTOLOGY 2023. [DOI: 10.1007/s00053-023-00686-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
|
|
19
|
Ye H, Li L, Dong Y, Zheng Q, Sha Y, Li L, Yang P, Jia Y, Gu J. Dysregulated low-density granulocyte contributes to early spontaneous abortion. Front Immunol 2023; 14:1119756. [PMID: 36911722 PMCID: PMC9995479 DOI: 10.3389/fimmu.2023.1119756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 02/13/2023] [Indexed: 02/25/2023] Open
Abstract
Spontaneous abortion (SA) is a common adverse pregnancy event with unclarified pathogenesis and limited therapeutic efficiency. Although most SA cases with the euploid embryo(s) are associated with immunological factors, the contribution of low-density granulocyte (LDG) in SA pathogenesis is rarely reported. This study aimed to investigate the serial characteristics and possible contribution of LDG and their subpopulations in early pregnancy, especially in early SA. Unpregnant (UP), normally pregnant (NP), and SA women were recruited, and the peripheral blood and endometrium/decidua were collected for LDG isolation and histological observation. The percentage, phenotype, and subpopulations of LDG were analyzed via flow cytometric analysis, and the ability of Nets formation was assessed by immunofluorescent and immunohistochemical assays. As a result, 43 participants were enrolled, including 10 UP, 15 NP, and 18 SA women. Compared with the UP group, the LDG percentage in peripheral blood mononuclear cells (PBMCs) and decidual immune cells (DICs) increased in the NP group, while the loss of this increase was observed in the SA group. Meanwhile, CD16int/- cell percentage in peripheral blood LDG (PB-LDG) increased in the NP and SA groups, and insufficient activation of CD16hi PB-LDG characterized by reduced CD11b expression was discovered in the SA group. Moreover, the LDG percentage in DICs was higher than that in PBMCs, and the decidual LDG (D-LDG) showed a surface marker expression profile that is easier to be activated in the pregnant cohort (NP + SA women). Finally, increased decidual Nets formation was observed in the SA group compared with the NP group, and more Nets formation was detected in D-LDG of NP and SA women following PMA stimulation. Overall, LDG participates in the maintenance of early pregnancy, while dysregulated LDG is responsible for early SA, providing novel potential targets for further exploration of SA pathogenesis and therapeutics.
Collapse
Affiliation(s)
- Hongxia Ye
- Department of Reproductive Immunology, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
- Department of Reproductive Immunology, Chengdu Jinjiang Hospital for Maternal & Child Health Care, Chengdu, Sichuan, China
- Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
| | - Lan Li
- Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yajun Dong
- Department of Reproductive Immunology, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
| | - Qu Zheng
- Department of Laboratory Medicine, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
| | - Yulin Sha
- Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
| | - Li Li
- Department of Gynecology, Sichuan Jinxin Women & Children Hospital, Chengdu, Sichuan, China
| | - Panyu Yang
- Department of Laboratory Medicine, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
| | - Yan Jia
- Department of Reproductive Immunology, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
- *Correspondence: Yan Jia, ; Jiang Gu,
| | - Jiang Gu
- Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Xi’nan Gynecology Hospital, Chengdu, Sichuan, China
- Department of Pathology and Pathophysiology, Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Center of Collaborative and Creative Center, Shantou University Medical College, Shantou, China
- *Correspondence: Yan Jia, ; Jiang Gu,
| |
Collapse
|
|
20
|
Integrated proteogenomic characterization of medullary thyroid carcinoma. Cell Discov 2022; 8:120. [DOI: 10.1038/s41421-022-00479-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 09/30/2022] [Indexed: 11/09/2022] Open
Abstract
AbstractMedullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.
Collapse
|
|
21
|
Yao J, Bergsland E, Aggarwal R, Aparicio A, Beltran H, Crabtree JS, Hann CL, Ibrahim T, Byers LA, Sasano H, Umejiego J, Pavel M. DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms. Oncologist 2022; 27:940-951. [PMID: 35983951 PMCID: PMC9632312 DOI: 10.1093/oncolo/oyac161] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 07/01/2022] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis. METHODS This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the potential for therapeutic targeting of DLL3, and ongoing studies of DLL3-targeting therapies. Classification, incidence, pathogenesis, and current management of NEN are reviewed to provide biological context and illustrate the unmet clinical needs. DISCUSSION DLL3 is overexpressed in many NENs, implicated in tumor progression, and is typically associated with poor clinical outcomes, particularly in patients with NEC. Targeted therapies using DLL3 as a homing beacon for cytotoxic activity mediated via several different mechanisms (eg, antibody-drug conjugates, T-cell engager molecules, CAR-Ts) have shown promising clinical activity in small-cell lung cancer (SCLC). DLL3 may be a clinically actionable target across NEN. CONCLUSIONS Current treatment options for NEN do not provide sustained responses. DLL3 is expressed on the cell surface of many NEN types and is associated with poor clinical outcomes. Initial clinical studies targeting DLL3 therapeutically in SCLC have been promising, and additional studies are expanding this approach to the broader group of NEN.
Collapse
Affiliation(s)
- James Yao
- Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emily Bergsland
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Rahul Aggarwal
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Ana Aparicio
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Himisha Beltran
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Judy S Crabtree
- Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Christine L Hann
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Toni Ibrahim
- Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCSS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Lauren A Byers
- Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | | | - Marianne Pavel
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| |
Collapse
|
|
22
|
Pavlidis ET, Pavlidis TE. Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update. World J Clin Cases 2022; 10:9573-9587. [PMID: 36186187 PMCID: PMC9516923 DOI: 10.12998/wjcc.v10.i27.9573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/16/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents (64Cu-DOTATATE or 68Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.
Collapse
Affiliation(s)
- Efstathios Theodoros Pavlidis
- Department of 2nd Surgical Propedeutic, Hippocration Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
| | - Theodoros Efstathios Pavlidis
- Department of 2nd Surgical Propedeutic, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki 54642, Greece
| |
Collapse
|
|
23
|
Lee L, Ramos-Alvarez I, Jensen RT. Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies. Cancers (Basel) 2022; 14:cancers14051250. [PMID: 35267558 PMCID: PMC8909561 DOI: 10.3390/cancers14051250] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Tumor resistance, both primary and acquired, is leading to increased complexity in the nonsurgical treatment of patients with advanced panNENs, which would be greatly helped by reliable prognostic/predictive factors. The importance in identifying resistance is being contributed to by the increased array of possible treatments available for treating resistant advanced disease; the variable clinical course as well as response to any given treatment approach of patients within one staging or grading system, the advances in imaging which are providing increasing promising results/parameters that correlate with grading/outcome/resistance, the increased understanding of the molecular pathogenesis providing promising prognostic markers, all of which can contribute to selecting the best treatment to overcome resistance disease. Several factors have been identified that have prognostic/predictive value for identifying development resistant disease and affecting overall survival (OS)/PFS with various nonsurgical treatments of patients with advanced panNENs. Prognostic factors identified for patients with advanced panNENs for both OS/PFSs include various clinically-related factors (clinical, laboratory/biological markers, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors. Particularly important prognostic factors for the different treatment modalities studies are the recent grading systems. Most prognostic factors for each treatment modality for OS/PFS are not specific for a given treatment option. These advances have generated several controversies and new unanswered questions, particularly those related to their possible role in predicting the possible sequence of different anti-tumor treatments in patients with different presentations. Each of these areas is reviewed in this paper. Abstract Purpose: Recent advances in the diagnosis, management and nonsurgical treatment of patients with advanced pancreatic neuroendocrine neoplasms (panNENs) have led to an emerging need for sensitive and useful prognostic factors for predicting responses/survival. Areas covered: The predictive value of a number of reported prognostic factors including clinically-related factors (clinical/laboratory/imaging/treatment-related factors), pathological factors (histological/classification/grading), and molecular factors, on therapeutic outcomes of anti-tumor medical therapies with molecular targeting agents (everolimus/sunitinib/somatostatin analogues), chemotherapy, radiological therapy with peptide receptor radionuclide therapy, or liver-directed therapies (embolization/chemoembolization/radio-embolization (SIRTs)) are reviewed. Recent findings in each of these areas, as well as remaining controversies and uncertainties, are discussed in detail, particularly from the viewpoint of treatment sequencing. Conclusions: The recent increase in the number of available therapeutic agents for the nonsurgical treatment of patients with advanced panNENs have raised the importance of prognostic factors predictive for therapeutic outcomes of each treatment option. The establishment of sensitive and useful prognostic markers will have a significant impact on optimal treatment selection, as well as in tailoring the therapeutic sequence, and for maximizing the survival benefit of each individual patient. In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed.
Collapse
Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
- National Kyushu Cancer Center, Department of Hepato-Biliary-Pancreatology, Fukuoka 811-1395, Japan
| | - Irene Ramos-Alvarez
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
- Correspondence: ; Tel.: +1-301-496-4201
| |
Collapse
|