Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.

ABSTRACT:

Purpose

The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC). Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to the next-generation ALK-TKI alectinib and potential strategies to overcome this resistance.

Experimental design

We established a cell line model of alectinib resistance, and analyzed a resistant tumor specimen from a patient who had relapsed on alectinib. We developed Ba/F3 models harboring alectinib-resistant ALK mutations and evaluated the potency of other next-generation ALK-TKIs i

SUBMITTER: Katayama R 

PROVIDER: S-EPMC4233168 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature