Pancreatic cancer remains one of the deadliest forms of cancer, with a five-year survival rate of less than 10% in the United States. Each year, about 64,000 Americans are diagnosed with the disease, and more than 50,000 die from it. Now, researchers in Spain report a promising new approach — a powerful three-drug combination that completely eliminated pancreatic cancer tumors in mice.

Treating pancreatic cancer is especially difficult because the symptoms are vague or nonexistent so it is often diagnosed at an advanced stage. The tumor’s deep location within the abdomen can make surgery challenging, and the cancer cells are frequently resistant to standard treatments such as chemotherapy and radiation. According to reports, the biology of pancreatic tumors also makes them particularly resistant to conventional therapies.

Most current drugs target KRAS, a genetic mutation found in about 90% of pancreatic cancer cases. While these treatments can initially slow tumor growth, resistance typically develops within months.

Researchers at Spain’s National Cancer Research Centre (CNIO) took a different approach. By attacking KRAS through three separate mechanisms at the same time, they were able to eliminate pancreatic tumors in mice with minimal side effects.

The study, published in Proceedings of the National Academy of Sciences (PNAS), found that the triple-drug strategy disrupted multiple KRAS signaling pathways simultaneously. The researchers combined an experimental KRAS inhibitor with a protein degrader and a drug already used to treat lung cancer. Together, the three agents led to the permanent disappearance of pancreatic tumors in animal models.

“These studies open a path to designing new combination therapies that can improve survival for patients with pancreatic ductal adenocarcinoma (the most common pancreatic cancer),” the study authors said in a statement. “These results point the way for developing new clinical trials.”

Mariano Barbacid, head of the Experimental Oncology Group at CNIO, said that while the findings are unprecedented, the research is still in its early stages.

“Although the results are extraordinary, we are not yet ready to begin clinical trials,” Barbacid noted. He added that the team’s success could help reshape the future of pancreatic cancer treatment by guiding the development of more effective combination therapies.