Mariano Barbacid Leads Triple-Drug Pancreatic Cancer Result in Mice, Raising Hopes for Hard-to-Treat Tumors
Mariano Barbacid is drawing fresh global attention after his research group in Madrid reported a striking preclinical result against pancreatic ductal adenocarcinoma, the most common and often most lethal form of pancreatic cancer. The work describes a three-drug strategy that eliminated tumors in mouse models designed to closely resemble the human disease, with no signs of treatment resistance for months after therapy stopped.
The finding is not a cure for people, but it is a notable step in a field where single-drug approaches have repeatedly fallen short.
What the new pancreatic cancer result showed
In the newly published peer-reviewed study, Barbacid’s team tested a combination therapy aimed at shutting down the cancer’s primary growth signal while also blocking common escape routes tumors use to survive. The regimen paired a next-generation KRAS-pathway inhibitor with two additional agents targeting EGFR and HER2 signaling, plus STAT3, a cellular stress-response pathway often associated with treatment persistence and relapse.
Researchers reported complete regression of pancreatic tumors in multiple laboratory settings, including engineered mouse models and models derived from patient tumors. They also reported durable control after treatment ended, with no evidence of tumors adapting around the blockade over an extended follow-up period.
Further specifics were not immediately available on how quickly this exact three-drug regimen could move into human testing, including the earliest possible trial start window and the initial dosing strategy.
Why KRAS is the central problem in pancreatic cancer
Pancreatic ductal adenocarcinoma is notorious for late detection, rapid spread, and resistance to many therapies. A key driver in most cases is KRAS, a mutated gene that acts like a stuck accelerator pedal, constantly signaling cells to grow.
Mechanistically, the challenge is that even when researchers inhibit the main KRAS-driven pathway, tumors can “rewire” by activating alternative signaling circuits. That is why combination approaches are increasingly prioritized: one drug slows the primary engine, while additional drugs close the detours and disable backup survival programs. In this case, the strategy is designed to prevent the tumor from escaping through EGFR and HER2 signaling and from leaning on STAT3-based stress survival when under pressure from treatment.
Some specifics have not been publicly clarified, including which side-effect patterns researchers consider most likely to become limiting factors once the approach is evaluated beyond animal models.
The drugs involved and what makes this approach different
The combination described in the research uses three distinct mechanisms rather than stacking variations of the same idea. One component is daraxonrasib, a KRAS-pathway agent that has also been studied clinically as a broader KRAS inhibitor approach beyond single-mutation targeting. The second component is afatinib, which inhibits EGFR and HER2, and the third is SD36, designed to disable STAT3 by promoting its degradation.
This matters because pancreatic cancer has a long history of responding briefly, then returning stronger. The goal here is not simply tumor shrinkage, but preventing the emergence of resistant cell populations that repopulate the cancer once therapy pressure eases.
Barbacid’s name carries added weight in this space because his career has been tightly tied to the genetic underpinnings of cancer. Decades ago, his early work helped establish how specific gene mutations can drive malignancy, and in later years he focused heavily on KRAS-driven tumors—an area long considered among the most stubborn targets in oncology.
Who is affected, and what patients should take from it now
This development will resonate most with pancreatic cancer patients and their families, who are often forced to navigate limited options and difficult prognoses. It also affects oncologists and trial centers, because credible preclinical durability can shape what combinations get prioritized for future clinical testing. Finally, it matters to drug developers and regulators, since multi-drug regimens must balance efficacy with tolerability, manufacturing, and clear safety monitoring plans.
The practical takeaway today is caution paired with cautious optimism: these results are compelling for research, but they do not yet prove safety or effectiveness in humans. Translating a durable animal-model response into real-world patient benefit typically requires staged clinical trials, careful dose finding, and clear evidence that side effects are manageable alongside standard care.
A next milestone comes soon in the scientific calendar: Barbacid is scheduled to present on targeted pancreatic cancer therapy at a February 3, 2026 conference event, which corresponds to 6:00 a.m. ET, as researchers and clinicians look for additional details on how the regimen was optimized and what steps could realistically follow.
