Differential unfolded protein response regulation in KRAS silencing sensitive and innately resistant colorectal cancer cells

Research Overview

Mutant-selective KRAS inhibitors produce limited, often short-lived responses in colorectal cancer, and the mechanisms letting tumor cells tolerate KRAS blockade are unclear. This study profiled early transcriptional and proteomic responses to KRAS silencing in 3D colorectal spheroid models, stratifying cell lines as sensitive (HCT116, SW480) or resistant (LS174T, SW837) by spheroid growth, cell cycle progression, and apoptosis.

Transcriptional profiling identified the unfolded protein response and WNT/β-catenin signaling as pathways specifically upregulated in association with resistance — candidate mechanisms for tolerance to KRAS inhibition and possible combination-therapy targets.