Triple‑drug KRAS combo erases pancreatic tumors in mice
A CNIO preclinical study reports a three‑drug regimen prevented resistance and eradicated pancreatic cancer in mice by targeting KRAS pathways—an important step for a cancer type that’s notoriously therapy‑resistant. The work highlights novel strategies to overcome adaptive tumor escape. (x.com)
A PNAS research article titled “A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance” lists Vasiliki Liaki and Sara Barrambana as first authors and Mariano Barbacid and Carmen Guerra as senior contributors; the manuscript was received August 25, 2025 and accepted November 3, 2025. (iris.unito.it) The experimental regimen combined RMC‑6236/daraxonrasib (a RAS(ON) inhibitor), the EGFR‑family tyrosine kinase inhibitor afatinib, and the STAT3 degrader SD36, designed to hit RAF1, EGFR and STAT3 signaling nodes. (iris.unito.it) The authors report that the triple combination induced complete regression in orthotopic KRAS/TP53‑mutant PDAC, produced significant shrinkage in genetically engineered mouse models and patient‑derived xenografts (PDX), and showed no tumor relapse for more than 200 days post‑treatment. (iris.unito.it) The study notes the drug combination was well tolerated in the preclinical experiments, with the authors explicitly recommending further work before human testing. (iris.unito.it) Lead investigator Mariano Barbacid and the CNIO team state they are not yet in a position to initiate clinical trials with this exact triple regimen, underscoring additional preclinical and regulatory steps are required. (cnio.es) Daraxonrasib (RMC‑6236) is being developed by Revolution Medicines and has received expedited regulatory designations and ongoing late‑stage clinical evaluation in pancreatic cancer, while daraxonrasib‑containing studies are listed on ClinicalTrials.gov (e.g., NCT07252232). (biospace.com) The CNIO paper acknowledges support from research funders and the CRIS Contra el Cáncer foundation opened a public fundraising campaign backing Barbacid’s work that attracted tens of thousands of donors; the authors also disclosed patent applications related to the triple‑therapy concept. (abc.es)
