Enhancing the Therapeutic Efficacy of KRAS^G12C Inhibitors in Lung Adenocarcinoma Cell Models by Cotargeting the MAPK Pathway or HSP90.

ABSTRACT:

Background

KRAS^G12C inhibitors have shown promising efficacy in early clinical trials, but drug resistance compromises their long-term benefits. Therefore, it is critical to understand the mechanisms of drug resistance and to design appropriate combinatory treatments to improve efficacy.

Methods

To understand the comprehensive mechanisms of drug resistance, we treated lung cancer cells with KRAS^G12C inhibitors for different periods and performed transcriptional profiling and signaling analysis to identify critical factors and pathways that drive drug tolerance and resistance. We also evaluated several drug combinations in vitro and in vivo to identify potentially effective therapeutics.

Results

We found that the feedback activation of multiple re

SUBMITTER: Liu Y 

PROVIDER: S-EPMC8632397 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature