Mutant and Wild-Type RAS Cross-talk and Stoichiometric Deficiencies Are Determinants of Sensitivity to Targeted Therapies in KRASG12R Pancreatic Ductal Adenocarcinoma.

doi:10.1158/0008-5472.CAN-25-0018

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Mutant and Wild-Type RAS Cross-talk and Stoichiometric Deficiencies Are Determinants of Sensitivity to Targeted Therapies in KRASG12R Pancreatic Ductal Adenocarcinoma.

Cancer research - 15 Apr 2026

Kamgar Mandana, Hobbs G Aaron, Davidson Raven, Dorbin Daniel, Herrera Juliannie, Langenheim John F, Burge Rachel A, Aldakkak Mohammed, Conrardy Ryan D, Szabo Aniko, Thalji Sam Z, Mayer Bradley, Grahl Justin J, Chung Brian Y, Phan Alexandria, Thomas James P, Seo Y David, Evans Douglas B, Christians Kathleen K, Erickson Beth, Hall William A, George Ben, Tsai Susan, Lytle Nikki K, Der Channing J, Kurzrock Razelle, McFall Thomas

Abstract excerpt

Therapies targeting the RAF-MEK-ERK pathway are generally considered to have limited efficacy in KRAS-mutant cancers. However, specific KRAS mutants exhibit distinct behaviors. Notably, KRASG12R pancreatic ductal adenocarcinoma (PDAC) tumors have shown sensitivity to MEK inhibitors (MEKi) in combination with autophagy inhibitors, but a better understanding of the underlying mechanisms is needed to optimize this...

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Identifiers

PMID: 41134578
DOI: 10.1158/0008-5472.CAN-25-0018
PMCID: PMC13080315

Genes

KRAS
HRAS
NF1
NRAS

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