Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Rev Clin Oncol. 2017 Sep;14(9):562-576. doi: 10.1038/nrclinonc.2017.40. Epub 2017 Apr 4.

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

Author information

1
Drug Resistance Group, Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK.
2
Northern Ireland Molecular Pathology Lab, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK.
3
University Paris Descartes, INSERM UMR-S1147, CNRS SNC 5014, Paris Sorbonne Cité Université, 45 rue des Saints-Pères 75006 Paris, France.
4
Department of Oncology, University of Torino, SP 142 km 3.95, 10060 Candiolo (TO), Italy.
5
Phase I - Early Clinical Trials Unit, Antwerp University Hospital; Wilrijkstraat 10, 2650 Edegem (Antwerp), Belgium.
6
Center for Oncological Research, University of Antwerp; Universiteitsplein 1, 2610 Wilrijk (Antwerp) Belgium.
7
Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.

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.

PMID:
28374784
DOI:
10.1038/nrclinonc.2017.40
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center