Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer.

doi:10.1038/s41591-026-04537-w

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Article

Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer.

Nature medicine - 1 Aug 2026

Aronchik Ida, Kar Sumit, Zhuang Yongxian, Ahler Ethan, Lai Lick Pui, Seshadri Vidya, Yang Yu Chi, Bulle Ashenafi, Menard Marie, Nayak Biswadeep, Labrecque Mark P, Dilly Julien, Kim Eejung, Jiang Lingyan, Yano Jason, Wasko Urszula N, Helland Ciara, Bredeson Sean, Garrick Brett, Gindin Yevgeniy, Sickler Brad, Wei Xing, Seamon Kyle, Jiang Jingjing, Lim Kian-Huat, Holderfield Matthew, Quintana Elsa, Hegde Aparna, Salman Zeena, Starodub Alexander, Spira Alexander, Park Wungki, Hong David S, Barve Minal, Pelster Meredith, Sommerhalder David, Punekar Salman R, Garrido-Laguna Ignacio, Wolpin Brian M, Maitra Anirban, Gustafson W Clay, Kelsey Steve, Smith Jacqueline A M, Lin Kevin K, Aguirre Andrew J, Singh Mallika

Abstract excerpt

Daraxonrasib is an orally bioavailable RAS(ON) multi-selective tri-complex inhibitor of the oncogenic mutant and wild-type variants of N, H and KRAS. We previously reported encouraging efficacy in a phase 1/2 clinical trial evaluating daraxonrasib monotherapy at clinically active dose levels in patients with previously treated, RAS mutant metastatic pancreatic adenocarcinoma (PDAC), providing the basis for...

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PMID: 42581230
DOI: 10.1038/s41591-026-04537-w
PMCID: PMC13472880

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KRAS
MYC

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