Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer
By A. Bardelli, S. Corso, A. Bertotti, S. Hobor, E. Valtorta, G. Siravegna, A. Sartore-Bianchi, E. Scala, A. Cassingena, D. Zecchin and 18 more. Cancer Discovery, 2013
633 citations recorded by the source corpus.
EGFR targeted monoclonal antibodies are effective in a subset of metastatic colorectal tumors (mCRC). Inevitably, all patients develop resistance, which occurs through emergence of KRAS mutations in approximately 50% of the cases. We show that amplification of the MET proto-oncogene is associated with acquired resistance in patients who do not develop KRAS mutations during anti-EGFR therapy. Amplification of the MET locus was present in circulating tumor DNA before relapse was clinically evident. Functional studies demonstrate that MET activation confers resistance to anti-EGFR therapy both in vitro and in vivo. Notably, in patient-derived CRC xenografts, MET amplification correlated with resistance to EGFR blockade which could be overcome by MET kinase inhibitors. These results highlight the role of MET in mediating primary and secondary resistance to anti-EGFR therapies in CRC and encourage the use of MET inhibitors in patients displaying resistance as a result of MET amplification.
Subfields: Cancer Research, Hepatology
View Paper: https://www.semanticscholar.org/paper/300aa63cc72913fffbf180e6693006231a431265
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In Cancer Research
Citations in the corpus
- Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research (2014, background): “In colorectal cancer, it has been shown that tumors resistant to EGFR inhibition harbor amplifications of other genes such as HER2 and MET (28, 44).”