KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells

The MET receptor tyrosine kinase is often deregulated in human cancers and several MET inhibitors are evaluated in clinical trials. Similar to EGFR, MET signals through the RAS-RAF-ERK/MAPK pathway which plays key roles in cell proliferation and survival. Mutations of genes encoding for RAS proteins, particularly in KRAS, are commonly found in various tumors and are associated with constitutive activation of the MAPK pathway. It was shown for EGFR, that KRAS mutations render upstream EGFR inhibition ineffective in EGFR-positive colorectal cancers.

Source: Molecular Oncology - April 13, 2015 Category: Cancer & Oncology Authors: Dominic Leiser, Michaela Medová, Kei Mikami, Lluís Nisa, Deborah Stroka, Andree Blaukat, Friedhelm Bladt, Daniel M. Aebersold, Yitzhak Zimmer Source Type: research