For half a century, pancreatic cancer has been one of medicine’s most stubborn failures. Treatments barely moved the needle. Survival rates stayed brutal. Resistance to drugs arrived fast and mercilessly.
Now, something unprecedented has happened.
Researchers in Spain report that pancreatic cancer tumors completely disappeared in mice, and stayed gone, using a three-drug combination designed to shut down the cancer’s core engine before resistance could even begin.
The study, published in Proceedings of the National Academy of Sciences (PNAS), comes from the National Cancer Research Centre (CNIO) and is led by legendary cancer biologist Mariano Barbacid, a pioneer of KRAS research.
The implications are enormous, even if human trials are still down the road.
Why Pancreatic Cancer Almost Always Wins
A team of scientists from the Spanish Cancer Research Centre, led by the renowned Dr Mariano Barbacid, has achieved the complete and permanent disappearance of pancreatic cancer in experimental models.
This discovery could make a difference in the fight against this disease. 👏 pic.twitter.com/gcnn1hPKBk
— Embassy of Spain UK (@EmbSpainUK) January 28, 2026
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is aggressive, silent, and usually detected late.
In Spain alone, more than 10,300 people are diagnosed each year. Across developed countries, the five-year survival rate remains below 10 percent.
The main culprit is KRAS, a mutated gene that drives cancer growth in about 90 percent of cases. Drugs that target KRAS were finally approved in 2021, but the celebration was short-lived.
Tumors adapted. Resistance emerged. The disease came roaring back within months.
Until now.
The Breakthrough Idea: Stop KRAS In Three Places At Once
Instead of blocking KRAS at a single point, the strategy that keeps failing, the CNIO team attacked the pathway at three separate molecular links.
Barbacid explains it with a simple image: a beam fixed to the ceiling at three points is far harder to break than one fixed at a single point.
In mice, that idea worked spectacularly.
By combining:
- an experimental KRAS inhibitor (daraxonrasib),
- an approved lung cancer drug (afatinib),
- and a protein degrader (SD36),
The researchers shut down the KRAS signaling network so thoroughly that pancreatic tumors regressed completely.
More importantly, they did not return.
No Resistance. No Major Toxicity. No Precedent.
The triple therapy was tested across three different mouse models of pancreatic ductal adenocarcinoma. In all of them, tumors vanished in a durable way.
Equally striking: the treatment caused no significant toxic side effects, a critical barrier that has derailed many aggressive cancer combinations in the past.
As the authors write in PNAS, the therapy “induces robust regression of experimental PDACs and avoids the onset of tumor resistance.”
That sentence alone explains why the oncology world is paying attention.
A Cure in Mice, But Not Yet in Humans
Barbacid is careful not to oversell the findings.
“We are not yet in a position to carry out clinical trials with this triple therapy,” he says, stressing that translating such complex combinations to patients will take time, optimization, and caution.
Still, after decades of stalled progress, this study does something rare in pancreatic cancer research: it changes the direction of the conversation.
For the first time, scientists have shown that resistance, long considered inevitable, can be designed out of the system.
Why This Moment Matters
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Pancreatic cancer has been called the “graveyard of drug development.” Many promising ideas die there.
This one did not.
While patients should not expect immediate treatments, the message from this study is clear: pancreatic cancer may not be unbeatable after all. It may simply require smarter, multi-layered attacks that leave the tumor nowhere to escape.
And after 50 years of frustration, that is news powerful enough to shake the field.
