Activation of KRAS Mediates Resistance to Targeted Therapy in MET Exon 14-mutant Non-small Cell Lung Cancer.

ABSTRACT:

Purpose

MET exon 14 splice site alterations that cause exon skipping at the mRNA level (METex14) are actionable oncogenic drivers amenable to therapy with MET tyrosine kinase inhibitors (TKI); however, secondary resistance eventually arises in most cases while other tumors display primary resistance. Beyond relatively uncommon on-target MET kinase domain mutations, mechanisms underlying primary and acquired resistance remain unclear.

Experimental design

We examined clinical and genomic data from 113 patients with lung cancer with METex14. MET TKI resistance due to KRAS mutation was functionally evaluated using in vivo and in vitro models.

Results

Five of 113 patients (4.4%) with METex14 had concurrent KRAS G12 mu

SUBMITTER: Suzawa K 

PROVIDER: S-EPMC6377821 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature