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Article

Distinct ERK and PI3K dependencies mediate a heterogeneous response to RAS(ON) inhibition in KRAS-mutant colorectal cancer.

Cell reports - 28 Jul 2026

Choi Philip H, Meredith Julia, Sharma Malvika, Chen Xiaoping, Qiu Juan, Markov Vladimir, de Stanchina Elisa, Singh Mallika, Rosen Neal

Abstract excerpt

RAS inhibitors have demonstrated limited efficacy in KRAS-mutant colorectal cancer (CRC). Here, we evaluate RMC-7977, a RAS(ON) multi-selective inhibitor, which shows a heterogeneous response in a panel of preclinical CRC models. Inhibition of PI3K signaling and cyclin D1 (CCND1) expression are strongly correlated with response. We find that stratifying tumors based on the ERK dependence of cyclin D1, mediated by...

Topics

Colorectal Neoplasms
Humans
Phosphatidylinositol 3-Kinases
Cyclin D1
Animals
Proto-Oncogene Proteins p21(ras)
Mutation
Cell Line, Tumor
Extracellular Signal-Regulated MAP Kinases
MAP Kinase Signaling System

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Apoptosis

Signal Transduction

Phosphoinositide-3 Kinase Inhibitors

Mice

Source

Identifiers

PMID: 42319820
DOI: 10.1016/j.celrep.2026.117559

Genes

KRAS
CCND1

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 29 Aug 2026. Prepared record publication-42319820-2026-08-29.1. Manifest publication-graph-cohort-2026-08-29.1.

Source receipt: PubMed via Helena Literature Corpus, retrieved 29 Aug 2026.

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