MADRID—Spanish researchers have achieved complete eradication of pancreatic tumors in mice using a novel triple-drug therapy, offering new hope against one of the deadliest cancers, according to a study published in the journal Proceedings of the National Academy of Sciences.
The breakthrough, led by Mariano Barbacid at the Spanish National Cancer Research Center (CNIO), targeted pancreatic ductal adenocarcinoma (PDAC), a disease that accounts for about 90% of pancreatic cancers and has a grim five-year relative survival rate of just 13% across all stages, per American Cancer Society data. For the most common form, adenocarcinoma, survival dips to 8%. In the U.S. alone, an estimated 67,440 new cases are projected for 2025, with 51,980 deaths, making it the third-leading cause of cancer mortality and on track to become second.
The study, detailed in the Proceedings of the National Academy of Sciences on Dec. 2, 2025, tested a combination of three drugs: daraxonrasib (also known as RMC-6236), a selective KRAS inhibitor; afatinib, an irreversible EGFR/HER2 kinase inhibitor already approved for lung cancer; and SD36, a selective STAT3 protein degrader.
👨🔬 Científicos españoles consiguen eliminar completamente el cáncer de páncreas gracias a la combinación de tres fármacos
👀 Un avance en modelos animales contra uno de los tumores más agresivos y con mayor tasa de mortalidad.
Toda la información aquí 🔗 https://t.co/T2xJQoKx9r pic.twitter.com/V3LTUkUbcw— elEconomista.es (@elEconomistaes) January 27, 2026
Pancreatic cancer often resists treatment due to mutations in the KRAS gene, which drives tumor growth in up to 95% of PDAC cases. Traditional therapies fail as tumors adapt and develop resistance. The CNIO team’s approach disrupts multiple KRAS signaling pathways simultaneously to block these escape routes.
Daraxonrasib inhibits the mutated KRAS protein directly, halting downstream signals that promote cell proliferation. Afatinib blocks upstream signals from EGFR family receptors, which can reactivate KRAS pathways. SD36 degrades STAT3, an orthogonal protein that supports tumor survival independently of KRAS. Together, this triad induces tumor cell senescence—a state of permanent growth arrest—leading to immune-mediated clearance without relapse.
In experiments, genetic models mimicking the therapy eradicated orthotopic PDAC tumors induced by KRAS and TP53 mutations in mice. The drug combination achieved full regression in three models: orthotopic transplants, genetically engineered mice, and patient-derived xenografts. No tumors recurred over 200 days post-treatment, with minimal side effects like mild weight loss or skin irritation.
Implications are profound for PDAC patients, who face limited options beyond surgery, chemotherapy and radiation. Only about 20% qualify for surgery at diagnosis, and even then, recurrence is common. The therapy could pave the way for human clinical trials, potentially improving outcomes for a cancer with stagnant survival rates despite advances in other oncology fields.
Experts caution that mouse models don’t always translate to humans, but the results build on emerging KRAS-targeted drugs.
“These findings should guide the development of new clinical trials that may benefit PDAC patients,” the study concluded.
The research was funded by multiple sources, including the CRIS Cancer Foundation, the European Research Council, Spain’s Agencia Estatal de Investigación (co-funded by the European Regional Development Fund), the European Union’s NextGenerationEU program, CIBERONC, the Instituto de Salud Carlos III, the Italian Cancer Research Association, and others. Barbacid holds an endowed chair from the AXA Research Fund.
Author: Lynnwood Times Staff
