Experimental Triple Therapy Eradicates Pancreatic Tumors in Mice Without Resistance

2026-01-29 general

Madrid, Thursday, 29 January 2026.
Researchers successfully eliminated pancreatic tumors in mice using a triple-drug regimen, keeping animals disease-free for over 200 days without the drug resistance typical in this aggressive cancer.

Breaking the Resistance Cycle

In a study published on January 26, 2026, in the Proceedings of the National Academy of Sciences (PNAS), a team led by Dr. Mariano Barbacid at the Spanish National Cancer Research Centre (CNIO) detailed a strategy that completely eliminated pancreatic ductal adenocarcinoma in mouse models [1][7]. The breakthrough relies on a triple-drug combination designed to block the KRAS oncogene—responsible for approximately 90% of pancreatic cancer cases—while simultaneously cutting off its escape routes [1][3]. The regimen utilizes daraxonrasib, a KRAS inhibitor; afatinib, a drug already approved for lung cancer that targets the EGFR protein; and SD36, a degrader of the STAT3 protein [1][3][8]. While drugs targeting KRAS were approved as early as 2021, their success has been historically limited by the tumor’s ability to develop resistance within months, a challenge this new multi-pronged approach appears to have overcome in preclinical testing [1].

Unprecedented Durability in Preclinical Models

The results observed in the laboratory offer a stark contrast to current clinical realities for a disease where the five-year survival rate remains below 10% [1][3]. In the study, the triple therapy was applied to various mouse models, including patient-derived xenografts (PDX) which utilize tissue from human pancreatic cancer patients [3][7]. The treatment induced robust tumor regression with no signs of disease recurrence for more than 200 days after the cessation of therapy [3][7]. Furthermore, the researchers reported that this significant efficacy was achieved without inducing relevant toxicities, suggesting the combination is well-tolerated in animal subjects [1][3]. Dr. Barbacid noted that this is the first time a complete, durable response with low toxicity has been achieved in these experimental models, marking a potential shift in how oncologists might approach this tumor type in the future [3][7].

From Bench to Bedside: The Regulatory Hurdle

Despite the promising data presented in Madrid on January 27, 2026, the path to human application remains complex [3][6]. Dr. Barbacid emphasized that the team is not yet in a position to initiate clinical trials with this specific triple cocktail [1][3]. While afatinib is commercially available, the other components face regulatory and development hurdles; for instance, while KRAS inhibitors are advancing, STAT3 degraders are still in earlier stages of the approval pipeline [3]. The study, funded by over 2 million euros from the Fundación CRIS Contra el Cáncer alongside European public funds, establishes a proof of concept that rational combination therapies can prevent the resistance mechanisms that currently make pancreatic cancer so deadly [1][3][7]. Experts suggest that while a KRAS inhibitor might be available for certain indications by 2027, optimizing this specific three-drug regimen for human patients will require further extensive research [3][8].

Sources

Biotech Oncology