Spanish Scientists Eliminate Pancreatic Cancer Tumors in Mice with Triple-Drug Therapy

Spanish researchers have successfully eradicated pancreatic cancer tumors in mice using an experimental combination of three drugs, according to a study published in Proceedings of the National Academy of Sciences. The research, led by biochemist Mariano Barbacid at Spain’s National Cancer Research Centre (CNIO), marks a significant step in pancreatic cancer research, though the therapy has not yet been tested in humans.

Pancreatic cancer is one of the deadliest forms of cancer globally, largely because it is difficult to detect early and highly resistant to treatment. Fewer than one in ten patients survive five years after diagnosis. In the study, the team focused on pancreatic ductal adenocarcinoma, the most common and aggressive type of the disease. The researchers treated mice with a combination of gemcitabine, all-trans retinoic acid (ATRA), and neratinib, which resulted in complete tumor disappearance. Remarkably, the cancer did not return even after therapy was stopped, an outcome rarely seen in pancreatic cancer models.

The treatment showed low toxicity, with mice tolerating it well, a critical factor in determining whether it can safely move to human trials. Each drug in the combination targets a different aspect of tumor survival: gemcitabine attacks rapidly dividing cancer cells, ATRA weakens the dense tissue that protects tumors, and neratinib blocks signals that promote tumor growth. By targeting multiple pathways simultaneously, the therapy prevents cancer cells from adapting and evading treatment.

The study concentrated on tumors driven by KRAS gene mutations, present in more than 90% of pancreatic cancer cases and historically considered difficult to treat. Despite the promising results in mice, experts caution that success in animal models does not guarantee similar outcomes in humans, where cancers are more complex and influenced by additional biological and environmental factors.

CNIO said the next stage of research will involve further validation and safety testing, with early-stage human trials possible if regulators approve. Barbacid, who identified the first human cancer gene in the 1980s, has spent decades studying KRAS-driven cancers, and his sustained focus has strengthened the study’s credibility within the global scientific community.