Targeting c-MET in gastrointestinal tumours: Rationale, opportunities and challenges

Conor A. Bradley, Manuel Salto-Tellez, Pierre Laurent-Puig, Alberto Bardelli, Christian Rolfo, Josep Tabernero, Hajrah A. Khawaja, Mark Lawler, Patrick G. Johnston, Sandra Van Schaeybroeck, MErCuRIC consortium

Research output: Contribution to journalReview article

Abstract

Data from many preclinical studies, including those using cellular models of colorectal, gastric, gastro-oesophageal and gastro-oesophageal junction cancers, indicate that the hepatocyte growth factor (HGF)-hepatocyte growth factor receptor (c-MET) pathway is vital for the growth, survival and invasive potential of gastrointestinal cancers. Following the availability of data from these various studies, and data on c-MET expression as a biomarker that indicates a poor prognosis in patients with gastrointestinal cancer and increased c-MET expression, inhibitors targeting this pathway have entered the clinic in the past decade. However, the design of clinical trials that incorporate the use of HGF/c-MET inhibitors in their most appropriate genetic and molecular context remains crucial. Recognizing and responding to this challenge, the European Commission funded Framework 7 MErCuRIC programme is running a biomarker-enriched clinical trial investigating the efficacy of combined c-MET/MEK inhibition in patients with RAS-mutant or RAS-wild-type metastatic colorectal cancer with aberrant c-MET expression. The design of this trial enables the continued refinement of the predictive biomarker and co-development of companion diagnostics. In this Review, we focus on advances in our understanding of inhibition of the HGF/c-MET pathway in patients with gastro-intestinal cancers, the prominent challenges facing the clinical translation and implementation of agents targeting HGF/c-MET, and discuss the various efforts, and associated obstacles to the discovery and validation of biomarkers that will enable patient stratification in this context.

Original languageEnglish
Pages (from-to)562-576
Number of pages15
JournalNature Reviews Clinical Oncology
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Targeting c-MET in gastrointestinal tumours: Rationale, opportunities and challenges'. Together they form a unique fingerprint.

  • Cite this

    Bradley, C. A., Salto-Tellez, M., Laurent-Puig, P., Bardelli, A., Rolfo, C., Tabernero, J., Khawaja, H. A., Lawler, M., Johnston, P. G., Van Schaeybroeck, S., & MErCuRIC consortium (2017). Targeting c-MET in gastrointestinal tumours: Rationale, opportunities and challenges. Nature Reviews Clinical Oncology, 14(9), 562-576. https://doi.org/10.1038/nrclinonc.2017.40