Triple-Drug Combo Stops Pancreatic Cancer in Mice

A new three-drug combination has wiped out pancreatic tumors in mice, offering real hope for a cancer that claims 87% of patients within five years of diagnosis.

Researchers at Spain's National Cancer Research Centre tested a treatment that blocks three cancer-growth pathways at once. The results, published in PNAS, showed something remarkable: the tumors didn't just shrink, they vanished completely.

"You couldn't even see where the tumor was," said senior study author Carmen Guerra, a cancer biologist at CNIO. "The pancreas was completely healthy."

Pancreatic cancer is notoriously deadly because it grows silently without symptoms until it has already spread. Nearly all cases involve a mutation in the KRAS gene, which gets stuck in the "on" position and fuels uncontrolled cell division.

The research team discovered that when they blocked KRAS-related pathways, tumors found a workaround through a protein called STAT3. So they designed a strategy to shut down all three escape routes simultaneously.

The triple therapy combines two existing drugs with a newer compound. Afatinib is already FDA-approved for lung cancer, while daraxonrasib is in clinical trials. The third drug specifically targets STAT3.

Scientists tested the combination in three different mouse models, including one using human tumor samples. In every case, the treatment eliminated tumors completely and kept them from returning for at least seven months, far longer than single-drug therapies achieve.

The Bright Side

What makes this breakthrough especially exciting is that the treatment caused no serious side effects in mice. The animals maintained normal body weight, blood counts, and organ health throughout treatment.

Standard chemotherapy attacks all rapidly dividing cells in the body, often causing severe damage while trying to control tumors. This targeted approach offers a potentially gentler path forward.

The team is already working on the next steps. They're developing improved versions of the drugs and testing them against other common KRAS mutations, since every patient's cancer is genetically unique.

Guerra acknowledges that mice tolerate treatments differently than humans do. One of the drugs, afatinib, already causes known side effects in people like skin and gastrointestinal issues. But the research opens a clear path toward designing clinical trials that could finally give patients with this devastating diagnosis better odds.

For the first time in pancreatic cancer research, scientists have found a way to stop tumors from adapting and fighting back.