Mariano barbacid

TL;DR:

CNIO researchers led by Mariano Barbacid cleared pancreatic tumors in mice.
The regimen combined a KRAS inhibitor with EGFR and STAT3 blockers.
Mice stayed cancer-free for over 200 days with low toxicity.
Results build on a December 2025 PNAS paper from the same group.
Human trials are not yet underway, but the path is clearer.

On January 27–29, 2026, multiple outlets in Spain and beyond reported that a team at Spain’s National Cancer Research Centre, CNIO, led by cancer biologist Mariano Barbacid, achieved complete regression of pancreatic ductal adenocarcinoma in mouse models. The study used a rational triple therapy that targets KRAS and two key signaling nodes that tumors use to escape treatment.

Coverage highlights that, after treatment, mice remained tumor-free for more than 200 days and showed no detectable toxicity, an unusual result for aggressive pancreatic cancer models. The work was supported by the CRIS Cancer Foundation and framed as a step toward clinical translation, pending further validation.

The science in plain language

Most pancreatic cancers are driven by mutations in the KRAS gene. These mutations act like a stuck accelerator for cell growth. Many drugs have tried to slow or block this engine, yet tumors often route around the block by switching to backup pathways.

Barbacid’s group tackled three points at once:

KRAS with daraxonrasib (also known as RMC-6236), a RAS(ON) multi-selective inhibitor.
EGFR/HER2 with afatinib, an irreversible kinase inhibitor that shuts down upstream signals.
STAT3 with SD-36, a degrader that removes a transcription factor linked to tumor survival.

In the experiments, the combination both shrank and then cleared tumors in mouse models engineered to mirror human pancreatic cancer. The regimen prevented resistance by blocking the main KRAS route, its upstream push, and an orthogonal survival pathway at the same time. These drug choices align with a peer-reviewed paper from December 2025 in the journal PNAS, which detailed the same triple strategy and reported complete, durable responses in mice.

How strong is the evidence?

Model choice. The team used orthotopic and patient-derived models that place tumors in the pancreas of mice, a stricter test than simple cell implants.
Durability. Disease remission held beyond 200 days in many mice, a long window for these models.
Safety signal. Reports describe low observed toxicity in animals.

Limits remain. Animal success does not guarantee human benefit. Doses, schedules, and side effects can change in people. Still, the results are stronger than many single-drug KRAS efforts, where resistance often appears within weeks. Coverage from Spanish and international outlets has stressed both the promise and the need for careful clinical steps.

Why it matters

Pancreatic ductal adenocarcinoma has one of the lowest five-year survival rates of all cancers. Patients often present late, surgery is possible for few, and standard regimens like FOLFIRINOX or gemcitabine-based combinations add months, not years. A combination that clears tumors in hard animal models without clear toxicity could reshape how researchers design trials and how drug makers prioritize pipelines. It also validates a clear idea for this disease, hit KRAS and its escape hatches together.

What happens next

Independent replication. Expect other labs to test the same drug trio or close variants, including alternatives to SD-36 as more STAT3 degraders and inhibitors enter preclinical pipelines.
Translational studies. Dose-finding and formulation work is needed. Daraxonrasib is in human trials for other settings, and afatinib is already approved for some cancers. A clinical-grade STAT3 agent that matches SD-36’s behavior will be key.
Patient selection. Early trials would likely enroll patients with KRAS-mutant tumors, then stratify by co-mutations such as TP53, CDKN2A, and SMAD4, which shape outcome and resistance.
Funding and partnerships. Moving from success in mice to a phase 1 trial requires sustained funding and industry partners. Recent CNIO communications stress the bridge between basic discovery and clinical testing.

Background on Mariano Barbacid

Barbacid is one of Spain’s most recognized cancer researchers. He isolated the first human oncogene, H-RAS, in 1982, led oncology drug discovery at Bristol-Myers Squibb, and founded the CNIO in Madrid in 1998. Since 2011 he has focused on KRAS-driven tumors, including lung and pancreas, producing a long line of mouse studies that mapped how KRAS signals and how to block it.

Quick guide: the regimen at a glance

Component	Target	Example agent used	Human status	Role in combo
KRAS blockade	KRAS signaling	Daraxonrasib, RMC-6236	In clinical trials	Shuts the main oncogenic driver
EGFR family	EGFR/HER2	Afatinib	Approved in other cancers	Cuts upstream growth signals
STAT3 pathway	STAT3	SD-36 (degrader)	Preclinical	Removes survival signaling node

Table based on the team’s PNAS description and media summaries of the CNIO results.

What readers should watch for

Protocol details. Look for dosing schedules and biomarkers in any future trial announcement.
Toxicity profile. Human safety will decide if the trio is viable.
Alternatives. If a clinical-grade STAT3 medicine differs from SD-36, trial outcomes could change.
Durability. The 200-day disease-free period in mice set a high bar. Trials will measure progression-free survival and circulating tumor DNA to see if deep responses translate.

Why it matters, in one minute

Pancreatic cancer kills fast and fights back. Barbacid’s team showed that shutting KRAS and its escape paths together can erase tumors in strict animal tests, for months, with little harm. That does not equal a cure for people today. It does hand clinicians a clearer, testable plan for tomorrow.

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