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

34 Citations (Scopus)

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

Fingerprint

Hepatocyte Growth Factor
Biomarkers
Gastrointestinal Neoplasms
Neoplasms
Clinical Trials
Proto-Oncogene Proteins c-met
Intestinal Neoplasms
Mitogen-Activated Protein Kinase Kinases
Esophageal Neoplasms
Molecular Biology
Colorectal Neoplasms
Stomach
Survival
Growth

ASJC Scopus subject areas

  • Oncology

Cite this

Bradley, C. A., Salto-Tellez, M., Laurent-Puig, P., Bardelli, A., Rolfo, C., Tabernero, J., ... 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

Targeting c-MET in gastrointestinal tumours : Rationale, opportunities and challenges. / Bradley, Conor A.; Salto-Tellez, Manuel; Laurent-Puig, Pierre; Bardelli, Alberto; Rolfo, Christian; Tabernero, Josep; Khawaja, Hajrah A.; Lawler, Mark; Johnston, Patrick G.; Van Schaeybroeck, Sandra; MErCuRIC consortium.

In: Nature Reviews Clinical Oncology, Vol. 14, No. 9, 01.09.2017, p. 562-576.

Research output: Contribution to journalReview article

Bradley, CA, Salto-Tellez, M, Laurent-Puig, P, Bardelli, A, Rolfo, C, Tabernero, J, Khawaja, HA, Lawler, M, Johnston, PG, Van Schaeybroeck, S & MErCuRIC consortium 2017, 'Targeting c-MET in gastrointestinal tumours: Rationale, opportunities and challenges', Nature Reviews Clinical Oncology, vol. 14, no. 9, pp. 562-576. https://doi.org/10.1038/nrclinonc.2017.40
Bradley, Conor A. ; Salto-Tellez, Manuel ; Laurent-Puig, Pierre ; Bardelli, Alberto ; Rolfo, Christian ; Tabernero, Josep ; Khawaja, Hajrah A. ; Lawler, Mark ; Johnston, Patrick G. ; Van Schaeybroeck, Sandra ; MErCuRIC consortium. / Targeting c-MET in gastrointestinal tumours : Rationale, opportunities and challenges. In: Nature Reviews Clinical Oncology. 2017 ; Vol. 14, No. 9. pp. 562-576.
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