An Activating KIT Mutation Induces Crizotinib Resistance in ROS1-Positive Lung Cancer.

ABSTRACT:

Introduction

Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) chromosomal rearrangements benefit from treatment with the ROS1 inhibitor crizotinib. Limited data exist on the spectrum of resistance mechanisms in ROS1-positive NSCLC. To delineate mechanisms of acquired resistance, we analyzed biopsy samples of tumor lesions that progressed while patients were receiving crizotinib.

Methods

An activating mutation in the KIT proto-oncogene receptor tyrosine kinase (KIT) (p.D816G) was identified by SNaPshot sequencing in a tumor sample from a patient with ROS1-positive NSCLC identified by fluorescence in situ hybridization whose disease progressed after initial response to crizotinib. In vitro studies included ev

SUBMITTER: Dziadziuszko R 

PROVIDER: S-EPMC4961521 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature