Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.

ABSTRACT:

Purpose

Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFR ^T790M-negative resistance.

Experimental design

We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M⁺) and -negative (T790M^-) disease.

Results

Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M^- tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic f

SUBMITTER: Chua KP 

PROVIDER: S-EPMC9401458 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature