Unprecedented experimental finding
Researchers from the Spanish National Cancer Research Centre (CNIO) have presented a study in Madrid showing how a therapy based on three inhibitor drugs induces complete and lasting regression of pancreatic ductal adenocarcinoma —the most common and aggressive type of pancreatic cancer— in genetically modified mice, without significant side effects and with a response that lasted more than 250 days in disease-free animals.
The work, funded by the Cris Against Cancer Foundation and published in the journal Proceedings of the National Academy of Sciences (PNAS), combines three compounds —daraxonrasib, afatinib, and SD36— that act simultaneously on key tumor mechanisms, managing to prevent the emergence of resistance and “pave the way for the design of new therapies that could improve the survival of human patients”.
A strategy that attacks multiple objectives
The triple therapy aims to interrupt the functioning of proteins essential for tumor growth and resistance, such as KRAS, EGFR, and STAT3, which act as engines for malignant cell development and spread.
Until now, these combined approaches had not been successfully achieved in pancreatic ductal adenocarcinomas, a cancer that in humans has a five-year survival rate of less than 5% and of which more than 10,300 new cases are diagnosed each year in Spain.
Limits and Steps Towards Clinical Trials
Despite the impact of the results in animal models, the researchers themselves emphasize that it is still **not possible to initiate clinical trials in humans** without completing essential preclinical research steps
Among the challenges is expanding the study to other mouse genetic models that represent different tumor subtypes, as well as incorporating a larger number of human tumor samples and studying metastases, which would allow for the identification of which patients could benefit from this therapy or adapted variants thereof.
Likewise, although one of the inhibitors could already be approved for certain indications in 2026 or 2027, further progress is still needed for the complete combination to reach safe clinical trials.
A Milestone in Oncological Research
The director of the Experimental Oncology Group at the CNIO, Mariano Barbacid, has highlighted that these results, although still preliminary for human use, represent a significant advance towards the development of effective treatments against pancreatic cancer, a tumor that is particularly difficult to treat due to its resistance and late diagnosis.
The research reinforces the need to continue betting on combined therapies and international scientific collaborations, as well as greater involvement from doctors and specialists in providing samples and data that allow these advances to evolve towards clinical applications.