Title: 
MET-driven resistance to dual EGFR and BRAF blockade may be overcome by switching from EGFR to MET inhibition in BRAF mutated colorectal cancer
Abstract: 

A patient with metastatic BRAF-mutated colorectal cancer initially responded to combined EGFR and BRAF inhibition with panitumumab plus vemurafenib. Pre-existing cells with increased MET gene copy number in the archival tumor tissue likely underwent clonal expansion during treatment, leading to the emergence of MET amplification in the re-biopsy taken at progression. In BRAF-mutated colorectal cancer cells, ectopic expression of MET conferred resistance to panitumumab and vemurafenib, which was overcome by combining BRAF and MET inhibition. Based on tumor genotyping and functional in vitro data, the patient was treated with the dual ALK-MET inhibitor crizotinib plus vemurafenib, thus switching to dual MET and BRAF blockade, with rapid and marked effectiveness of such strategy. Although acquired resistance is a major limitation to the clinical efficacy of anticancer agents, the identification of molecular targets emerging during the first treatment may afford the opportunity to design the next-line of targeted therapies, maximizing patient benefit.

Publication Date: 
Lunedì, Giugno 20, 2016
PMID: 
27325282

 

Raggiungi l'Istituto di Candiolo

 
Come raggiungere l'Istituto di Candiolo

 

  •  Indirizzo per navigatori: Strada Provinciale 142 di Piobesi incrocio Strada Statale 23 del Sestriere

  •  Coordinate per navigatori: 44°58'01.6"N 7°34'00.0"E