A study led by the Experimental Oncology Group at the Spanish National Cancer Research Centre (CNIO) has described a triple-combination therapy for pancreatic cancer. The work has been published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS).

The study shows that genetic ablation of three key nodes in KRAS signaling (RAF1, EGFR, and STAT3) leads to complete and permanent regression of orthotopic PDAC tumors driven by KRAS/TP53 mutations. Similarly, a drug combination targeting KRAS (RMC-6236/daraxonrasib), EGFR (afatinib), and STAT3 (SD36) induces full tumor regression with no resistance observed for over 200 days. This triple therapy proved effective in both genetically engineered mouse models and patient-derived xenografts, without tumor relapse. Importantly, the treatment was well tolerated. Although the findings support the development of clinical trials based on this combined strategy to improve PDAC therapy, alternatives to afatinib and SD36 will be needed to facilitate clinical translation by reducing toxicity and improving ADME properties, respectively.

This finding opens the door to exploring these therapeutic avenues and guiding the development of new clinical trials that could benefit patients with pancreatic ductal adenocarcinoma.

Link to ➡️ Full article

Links to Research group ➡️ Experimental Oncology ALIPANC, Experimental Oncology CNIO.