Why This Pancreatic Cancer Study Is Turning Heads in Oncology

For decades, pancreatic cancer has defied targeted therapies by rapidly evolving escape mechanisms. In a new study, Spanish researchers report that a carefully designed three-drug strategy shut down those escape routes entirely in laboratory models, producing complete and durable tumor regression.

Headlines over the last few days have screamed that pancreatic cancer has been “cured.” The truth is more nuanced, but it’s real, important, and worth paying close attention to. A Spanish team led by Mariano Barbacid has published preclinical results showing a three-drug combination that eliminated pancreatic tumours in multiple mouse models and prevented the tumor resistance that has plagued earlier KRAS-targeted efforts. This is not a human cure yet,  but it is a meaningful leap forward in a field that has struggled for decades.

What The Team Actually Reported (The Key Experimental Findings)

The published study (Proceedings of the National Academy of Sciences (PNAS), tested a triple combination of,

• Daraxonrasib- an experimental KRAS(ON) inhibitor (targets the common oncogenic driver in ~90% of pancreatic ductal adenocarcinomas).

  
  

• Afatinib- an approved irreversible EGFR/HER2 kinase inhibitor (repurposed here to block parallel growth signaling).

  
  

• SD36- a PROTAC (protein degrader) that targets STAT3 for destruction (STAT3 is a key escape/backup pathway tumors use).

In three independent mouse models- including genetically engineered models and patient-derived xenografts (PDX)- the triple therapy induced complete tumour regression and no detectable recurrence during the observation window (reported as ~200 days in some summaries). Treated mice showed no major toxic effects in the reported experiments.

Mechanistic insight- blocking multiple signalling nodes simultaneously (KRAS signaling + EGFR/HER2 + STAT3) appears to prevent the rapid adaptive resistance that single-agent KRAS inhibitors often provoke. In short, the tumor’s usual “escape routes” were sealed off at once.

Why is it different from previous KRAS work? Today’s KRAS inhibitors have shown clinical promise, but tumors frequently adapt by activating alternative pathways (EGFR, STAT3, etc.). The Barbacid group's approach is deliberately multi-target, instead of chasing a single Achilles’ heel, it simultaneously disables multiple survival circuits so the tumor has nowhere easy to escape. The mouse data show that the strategy can work durably, at least in those models.

But Exactly Who Is Mariano Barbacid?

Mariano Barbacid is a highly established cancer biologist with a long track record,

• Ph.D. from Universidad Complutense (Madrid), postdoc at the US National Cancer Institute (NCI).

  
  

• Famous for isolating the first human oncogene (H-Ras) and identifying the mutation responsible for its transforming activity (Nature, 1982), a foundational discovery in molecular oncology.

  
  

• Long academic career, leadership at the Spanish National Cancer Research Centre (CNIO), prior industry experience (Bristol-Myers Squibb), multiple honours and advisory roles.

  
  

Barbacid is not a fringe figure, he is a senior, mainstream scientist whose work has shaped the RAS field for decades. That pedigree matters when a lab claims something as striking as complete tumor elimination in models.

Funding And Institutional Backing For The Study

The work was carried out at the Spanish National Cancer Research Centre (CNIO) and lists a range of institutional and philanthropic supporters. Fundación CRIS Contra el Cáncer, the European Research Council (ERC), the Spanish State Research Agency (co-financed by ERDF / Next Generation EU), CIBERONC, and the Carlos III Health Institute. CNIO’s press statement and related materials list these funders explicitly.

Fundación CRIS has publicly stated (press material) that it has supported Barbacid’s project since ~2020 and that cumulative funding for his program surpasses €2 million, a concrete sign of philanthropic investment behind the research.

Why funding matters here- rigorous, reproducible preclinical studies require sustained resources (animal models, medicinal chemistry/compound access, toxicology, staff). Backing from respected public and philanthropic sources increases confidence that the work met accepted standards and was not an under-resourced one-off.

What The Laboratory Models Actually Mean, Strengths, And Limits

 Pancreatic tumors eradicated in multiple experimental models using a strategy designed to block resistance before it begins.

Strengths

• Multiple orthogonal models (genetically engineered mice and PDX) raise confidence that the effect is not an oddity of one model. PDX models bring human tumor tissue into an in vivo setting, improving translational relevance compared with cell lines alone.

  
  

• Durability (no recurrence during long observation windows in mice) and apparent tolerability are encouraging starting points for therapy design.

  
  

Limitations

• Physiology and pharmacology differ. Drug exposures, metabolism, immune context, and tumor microenvironments in mice are not identical to those in humans, a treatment well-tolerated in mice can still have unacceptable toxicity in humans, or fail because of pharmacokinetic differences.

  
  

• Tumour heterogeneity. Human pancreatic tumors are genetically and microenvironmentally heterogeneous; a regimen that works across the tested models may still fail in subsets of patients with different mutations or microenvironments.

  
  

• PROTACs and translation. SD36 is an experimental research PROTAC that degrades STAT3. PROTAC pharmacology in humans is still an area of active development, safety, dosing, and off-target degradation must be characterized.

  
  

The data represent a major preclinical advance, not immediate clinical practice. The standard path now is expanded preclinical toxicology, dose optimization, and early-phase human trials, typically over several years. CNIO and Barbacid’s team have signaled that clinical translation is the goal, but not immediate.

Public Reaction And Online Controversy

Celebration and hype: Mass media and charities have amplified the news (headlines like “cure” in mice), and advocacy groups have expressed excitement because pancreatic cancer has very poor survival rates and huge unmet needs.

Skepticism and caution: Science journalists, clinicians, and researchers have repeatedly cautioned that “cured in mice” is not the same as “cured in humans.” Responsible reporting stresses the need for clinical trials and the many historical examples where mouse success did not translate. Livescience and other outlets emphasized this nuance.

Unhelpful social blowback: Some online response has been petty or irrelevant,  for example, viral posts mocking Barbacid’s appearance rather than engaging with the science. Several outlets called out that social media focused on superficial commentary rather than substance. That kind of reaction distracts from public understanding.

Misinformation risk: Headlines that omit “in mice” or treat the finding as an immediate cure create unrealistic expectations for patients and families. Trusted sources are therefore emphasizing careful language, “major preclinical advance” or “promising in animal models” rather than “cure.”

What Will Be Required To Move From Mice → Patients

1. Expanded preclinical safety/toxicology for the triple combo (especially the PROTAC) in at least two species, including dose-finding and off-target profiling.

   
   

2. Pharmacokinetic and pharmacodynamic (PK/PD) work to ensure proper exposures in humans and to define biomarkers of on-target activity (e.g., suppressed pERK, STAT3 levels).

   
   

3. Phase 1 human trials for safety and initial signs of efficacy, likely starting with advanced patients who have no standard options. Trials must be designed to monitor toxicity and early signals carefully.

   
   

4. Patient selection strategies for pancreatic tumors vary, biomarker-guided patient selection could maximize the chance of seeing benefit.

CNIO has said that clinical translation is the objective, but that regulatory, financing, and technical steps will take time. Some press pieces suggest an optimistic timeline of a few years to first trials if funding and regulatory steps progress smoothly, but timelines in oncology are often longer.

Bottom Line, Cautious Optimism, Not Instant Celebration

This work, led by Mariano Barbacid and his CNIO colleagues, is a substantial and credible preclinical advance, a cleverly designed triple therapy eliminated pancreatic tumors in multiple mouse models and prevented the resistance that has foiled prior single-agent strategies. It’s different because it addresses tumor adaptation by combining a KRAS inhibitor with blockers/degraders of the major escape routes.

That said, “promising in mice”, ≠ “cure for people”. The translation hurdles, PK/PD, toxicity, tumor heterogeneity, and manufacturing/clinical trial logistics (especially with experimental PROTACs), remain real. If you are a patient or caregiver, discuss any headlines or potential trials with your oncology team; they are best placed to interpret clinical relevance and trial eligibility.

References

• V. Liaki, S. Barrambana, M. Kostopoulou, C.G. Lechuga, E. Zamorano-Dominguez, D. Acosta, L. Morales-Cacho, R. Álvarez, P. Sun, B. Rosas-Perez, R. Barrero, S. Jiménez-Parrado, A. López-García, M. San Roman, J.C. López-Gil, M. Drosten, B. Sainz, M. Musteanu, E. Caleiras, N. Dusetti, V. Poli, F. Sánchez-Bueno, C. Guerra, & M. Barbacid, A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance, Proc. Natl. Acad. Sci. U.S.A. 122 (49) e2523039122, https://doi.org/10.1073/pnas.2523039122 (2025).

  
  

• CNIO press release: The group led by Barbacid at CNIO completely eliminates pancreatic tumours in mice.