Acquired Resistance to KRAS^G12C Inhibition in Cancer.

ABSTRACT:

Background

Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS^G12C). The mechanisms of acquired resistance to these therapies are currently unknown.

Methods

Among patients with KRAS^G12C -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS^G12C inhibitors.

Results

A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1

SUBMITTER: Awad MM 

PROVIDER: S-EPMC8864540 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature