Triple Combination Therapy Induces Complete Pancreatic Cancer Regression

Researchers at the Spanish National Cancer Research Centre (CNIO) have announced a potential breakthrough in treating one of the world's deadliest diseases. A new study reveals that a triple combination therapy can induce the complete and permanent regression of pancreatic tumours in preclinical models, effectively overcoming the treatment resistance that usually makes this cancer so lethal.

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is notorious for its poor survival rate—less than 10 percent after five years in Spain. The difficulty lies in the cancer’s ability to quickly develop resistance when only one pathway is blocked.

To combat this, the CNIO team developed a "triple inhibition strategy" that simultaneously targets three critical nodes in the KRAS signalling pathway: RAF1 (downstream), EGFR (upstream), and STAT3 (orthogonal/parallel). This multi-pronged approach prevents the tumour from finding alternative survival routes.

The treatment involves a specific trio of drugs: RMC-6236 (daraxonrasib): An experimental inhibitor targeting KRAS. Afatinib: An EGFR family inhibitor already approved for lung cancer. SD36: A selective STAT3 protein degrader.

When tested in advanced mouse models, the therapy did more than just reduce tumour size; it stopped growth entirely. Remarkably, there was no evidence of tumour resistance for more than 200 days following the treatment. Furthermore, the therapy was well-tolerated by the subjects, suggesting a favorable safety profile for future human application.

While these results are a significant milestone, experts urge caution. Researchers noted that the study was conducted on mouse models and human cancer tissues grown in labs (PDX), meaning more research is required before human trials can begin. Optimizing this combination for patients will be a complex process, but these findings provide a clear roadmap for the development of new clinical trials that could finally improve survival rates for PDAC patients.

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🔖 Sources

Drug trio found to block tumour resistance in pancreatic cancer models

Drug trio found to block tumour resistance in pancreatic cancer

Scientists achieve pancreatic tumour regression in breakthrough study

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Keywords: Complete Pancreatic Cancer Regression

Complete Pancreatic Cancer Regression

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