Development of a Novel c-MET-Based CTC Detection Platform.

Abstract

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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Citation

Published Version (Please cite this version)

10.1158/1541-7786.MCR-16-0011

Publication Info

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

Zhang

Tian Zhang

Adjunct Associate Professor in the Department of Medicine
Strickler

John Strickler

Professor of Medicine
Abbruzzese

James Abbruzzese

D. C. I. Distinguished Professor of Medical Oncology

My research interests include the clinical study and treatment of pancreatic cancer.

Harrison

Michael Roger Harrison

Associate Professor of Medicine
George

Daniel James George

Eleanor Easley Distinguished Professor in the School of Medicine
Hurwitz

Herbert Ira Hurwitz

Adjunct Professor in the Department of Medicine

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

Armstrong

Andrew John Armstrong

Professor of Medicine

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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