Sotorasib resistance triggers epithelial-mesenchymal transition and activates AKT and P38-mediated signaling.

ABSTRACT:

Background

The molecular non-genetic changes of resistance to sotorasib are currently uncertain. The aim of this study was to generate a sotorasib-resistant cell line via selective pressure and systematically examine the molecular and phenotypic alterations caused by resistance.

Methods

Mutant NCI-H358 (KRAS^G12C) were exposed to incremental doses (2-512 nM) of sotorasib. Then, resistant clones were separated by single-cell sorting. Proliferation was analyzed in real-time by xCELLigence; protein profiles were quantified by protein arrays; and mRNA expression profile was measured using the PanCancer Pathways panel by NanoString. In silico analyses were conducted from a database comprising patient-derived xenograft (PDX) models and cell lines resistant to soto

SUBMITTER: Megid RA 

PROVIDER: S-EPMC11821485 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature