Drug trio found to block tumour resistance in pancreatic cancer

Summary

Drug trio found to block tumour resistance in pancreatic cancer A new study reports that a triple-targeted drug combination can drive complete and lasting regression of pancreatic tumours in preclinical models, potentially overcoming treatment resistance in one of the deadliest cancers. Researchers at the Spanish National Cancer Research Centre have announced a potential breakthrough combination therapy that induces complete regression of pancreatic tumours and prevents tumour resistance in preclinical models. The study describes a targeted combination therapy that simultaneously targets three key signalling pathways in pancreatic ductal adenocarcinoma (PDAC), the most common and lethal type of pancreatic cancer. Triple inhibition strategy Pancreatic cancer remains notoriously difficult to treat, with very poor survival rates and limited effective therapies. The new research aims to combat this by targeting RAF1, EGFR family receptors and STAT3 signalling – nodes that are crucial for tumour growth and survival. According to the authors, “genetic ablation of three independent nodes involved in downstream (RAF1), upstream (EGFR) and orthogonal (STAT3) KRAS signalling pathways leads to complete and permanent regression of orthotopic PDACs induced by KRAS/TP53 mutations.” The triple treatment combines three drugs: RMC-6236 (daraxonrasib): targeting KRAS Afatinib: an EGFR family inhibitor SD36: a selective STAT3 degrader These agents together were tested in orthotopic mouse models of PDAC, where tumour cells are implanted in a location that closely resembles their natural environment in the pancreas. The results demonstrated the therapy not only reduced tumour size but also entirely stopped tumour growth with no evidence of tumour resistance for more than 200 days after treatment. Broad efficacy in preclinical models Researchers extended their observations beyond engineered mouse models. The combination therapy also led to significant regression in genetically engineered...