SCIENTISTS ELIMINATED PANCREATIC CANCER IN MICE WITH 3 DRUGS
In December 2025, a team of scientists in Spain successfully eliminated pancreatic cancer in mice using a novel three-drug combination. The researchers at the National Cancer Research Center (CNIO) in Madrid, led by biochemist Mariano Barbacid, managed to destroy the tumors completely without the cancer developing a resistance to the treatment.
The breakthrough study was published in the Proceedings of the National Academy of Sciences on December 9, 2025. The research appeared in volume 122, issue 49 of the journal. Titled “A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance,” the project focused entirely on pancreatic ductal adenocarcinoma.
Also known as PDAC, this is the most common form of pancreatic cancer and one of the most deadly. Worldwide, the five-year survival rate is only 10 percent. The pancreas is an oblong organ tucked behind the stomach that produces digestive enzymes and releases hormones to regulate blood sugar. When cancer develops there, it is notoriously difficult to treat. According to the University of Texas MD Anderson Cancer Center, cited by Our Cancer Stories, risk factors for the disease include being male, older age, smoking, obesity, and being African American.
Targeting three pathways at once
A major hurdle in treating pancreatic tumors is that they develop resistance to medication quickly. When a drug successfully blocks one of the cancer’s growth pathways, the tumor typically finds an alternative route and continues to spread. To circumvent this problem, the CNIO team decided to attack the cancer from three different directions simultaneously.
Their experimental treatment combined two established drugs, afatinib and daraxonrasib, with a compound known as SD36. Daraxonrasib, which is also called RMC-6236, works as a KRAS inhibitor. Afatinib inhibits the EGFR-family kinases, and SD36 degrades a protein called STAT3. By targeting all three signaling nodes at once, the therapy blocked the cancer’s ability to use alternative growth pathways.
The researchers tested the three-drug combination on three different mouse models. According to ARA, these included mice with implanted tumor cells, genetically modified mice, and mice carrying human cancer cells.
The results showed significant and lasting tumor regression across the models. In one experiment, 16 out of 18 treated mice saw their tumors disappear completely, with no relapse observed during an 80-day window. In another model with orthotopic mouse tumors, the animals survived with complete tumor regression and no signs of resistance for at least 250 days.
“This study describes a triple combination therapy […] that induces the robust regression of experimental PDACs and avoids the onset of tumor resistance,” the study authors wrote, according to a release by CNIO.
Historically, aggressive combination therapies have been too toxic for the body to handle. However, the researchers found that the mice tolerated the triple treatment well. The animals maintained their tissue integrity, kept normal blood cell counts, and did not suffer from weight loss.
Barbacid, who led the project as the head of CNIO’s Experimental Oncology Group, is a prominent figure in cancer genetics. He is widely known for isolating the first human oncogene, HRAS, in 1982. In 2020, he received the Echegaray Medal, the highest scientific honor awarded by Spain’s Royal Academy of Exact, Physical and Natural Sciences, for his work in cancer research.
Despite the unprecedented success in preclinical models, the treatment is not yet ready for human patients. In an update to the CNIO website on October 31, 2026, the center reiterated that the research team is not in a position to conduct clinical trials just yet.
“[A]lthough experimental results like those described here have never been obtained before, we are still not in a position to carry out clinical trials with the triple therapy,” Barbacid said.
