MET Alterations Are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer.

ABSTRACT:

Purpose

Most ALK-positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors. MET amplification has been described in patients progressing on ALK inhibitors, but frequency of this event has not been comprehensively assessed.

Experimental design

We performed FISH and/or next-generation sequencing on 207 posttreatment tissue (n = 101) or plasma (n = 106) specimens from patients with ALK-positive lung cancer to detect MET genetic alterations. We evaluated ALK inhibitor sensitivity in cell lines with MET alterations and assessed antitumor activity of ALK/MET blockade in ALK-positive cell lines and 2 patients with MET-driven resistance.

Results

MET amplification was detec

SUBMITTER: Dagogo-Jack I 

PROVIDER: S-EPMC7269872 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature