Development of a Novel c-MET-Based CTC Detection Platform.
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2016-06
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UNLABELLED: Amplification of the MET oncogene is associated with poor prognosis, metastatic dissemination, and drug resistance in many malignancies. We developed a method to capture and characterize circulating tumor cells (CTC) expressing c-MET using a ferromagnetic antibody. Immunofluorescence was used to characterize cells for c-MET, DAPI, and pan-CK, excluding CD45(+) leukocytes. The assay was validated using appropriate cell line controls spiked into peripheral blood collected from healthy volunteers (HV). In addition, peripheral blood was analyzed from patients with metastatic gastric, pancreatic, colorectal, bladder, renal, or prostate cancers. CTCs captured by c-MET were enumerated, and DNA FISH for MET amplification was performed. The approach was highly sensitive (80%) for MET-amplified cells, sensitive (40%-80%) for c-MET-overexpressed cells, and specific (100%) for both c-MET-negative cells and in 20 HVs. Of 52 patients with metastatic carcinomas tested, c-MET CTCs were captured in replicate samples from 3 patients [gastric, colorectal, and renal cell carcinoma (RCC)] with 6% prevalence. CTC FISH demonstrated that MET amplification in both gastric and colorectal cancer patients and trisomy 7 with gain of MET gene copies in the RCC patient. The c-MET CTC assay is a rapid, noninvasive, sensitive, and specific method for detecting MET-amplified tumor cells. CTCs with MET amplification can be detected in patients with gastric, colorectal, and renal cancers. IMPLICATIONS: This study developed a novel c-MET CTC assay for detecting c-MET CTCs in patients with MET amplification and warrants further investigation to determine its clinical applicability. Mol Cancer Res; 14(6); 539-47. ©2016 AACR.
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Zhang, Tian, Rengasamy Boominathan, Brad Foulk, Chandra Rao, Gabor Kemeny, John H Strickler, James L Abbruzzese, Michael R Harrison, et al. (2016). Development of a Novel c-MET-Based CTC Detection Platform. Mol Cancer Res, 14(6). pp. 539–547. 10.1158/1541-7786.MCR-16-0011 Retrieved from https://hdl.handle.net/10161/11944.
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Scholars@Duke
Tian Zhang
John Strickler
John Strickler, MD is a Professor of Medicine in the Division of Medical Oncology, where he is Co-Leader for the Precision Cancer Medicine and Investigational Therapeutics Program at the Duke Cancer Institute, Leader of the Molecular Tumor Board, and Associate Director of Clinical Research – GI Oncology. Dr. Strickler’s clinic specializes on the treatment of gastrointestinal malignancies, with a particular emphasis on gastroesophageal, pancreatic, and colorectal cancers. His research focuses on precision cancer medicine: identification of biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy. He has designed and executed clinical trials that test novel therapies and innovative therapeutic strategies. He was Principal Investigator on an investigator sponsored trial that led to the first FDA-approved therapy for HER2+ metastatic colorectal cancer. He has first-author publications in several high impact factor medical journals, including the New England Journal of Medicine, Clinical Cancer Research, Cancer Discovery, Journal of Clinical Oncology, and Lancet Oncology. Nationally, he has served as a member of the American Society of Clinical Oncology (ASCO) Treatment Guidelines Committee for Advanced Colon Cancer.
James Abbruzzese
My research interests include the clinical study and treatment of pancreatic cancer.
Michael Roger Harrison
Daniel James George
Herbert Ira Hurwitz
Particular Clinical Interests and Skills: Phase I clinical trials involving new anti cancer drugs; drug combinations; and combinations of new drugs with radiation; cancers of the GI system
Andrew John Armstrong
I am a clinical and translational investigator focused on precision therapies and biomarkers in advanced prostate and other GU cancers. I oversee a large research team of clinical and lab based investigators focused on improving patient outcomes, preventing metastatic disease, and understanding the biology of aggressive prostate cancer. Some key themes:
1. Predictors of sensitivity and clinical efficacy of therapies in advanced prostate cancer
2. Novel designs of clinical trials and pharmacodynamic/translational studies in prostate, kidney, bladder cancer
3. Pre-operative models for drug development of novel agents in human testing in prostate cancer
4. Novel therapies and drug development for prostate, renal, bladder, and testicular cancer
5. Design of rational combination therapies in men with metastatic hormone-refractory prostate cancer
6. Developing prognostic and predictive models for progression and survival in metastatic prostate cancer
7. Examining surrogate markers of mortality in metastatic prostate cancer
8. Clear cell and non-clear cell renal cell carcinoma: natural history, sensitivity to novel agents including mTOR and VEGF inhibition
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