NIH R01 · 2025
Proteostasis Reprogramming in Mutant KRAS-Driven Cancers
ABSTRACT KRAS is one of the most frequently mutated genes in human cancers. Despite advances in the development of inhibitors that directly target mutant KRAS and the FDA approval of KRASG12C inhibitor sotorasib for KRASG12C- mutant non-small cell lung cancer (NSCLC), cancer cell adaptation and resistance to KRAS inhibitors are almost inevitable and remains a major challenge that limits their clinical benefits. Our preliminary data establish proteostasis reprogramming as an essential mechanism that mediates tumor resistance to KRAS inhibitor. Inactivation of oncogenic KRAS rapidly downregulates both the heat shock response (HSR) and IRE1a branch of the unfolded protein response (UPR).…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.