Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer.

ABSTRACT:

Purpose

Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small-molecule ALK inhibitor. Unfortunately, not every patient responds and acquired drug resistance inevitably develops in those who do respond. This study aimed to define molecular mechanisms of resistance to crizotinib in patients with ALK(+) non-small cell lung cancer (NSCLC).

Experimental design

We analyzed tissue obtained from 14 patients with ALK(+) NSCLC showing evidence of radiologic progression while on crizotinib to define mechanisms of intrinsic and acquired resistance to crizotinib.

Results

Eleven patients had material evaluable for molecular analysis. Four patients (36%) developed secondary mutations in the tyrosine kinase domain

SUBMITTER: Doebele RC 

PROVIDER: S-EPMC3311875 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature