Researches have presented a new treatment strategy for pancreatic ductal adenocarcinoma (PDAC), a highly aggressive cancer with a survival rate of about 13%. While most PDAC cases have KRAS mutations, around 22% also lose the MTAP gene. This MTAP deletion causes a buildup of a molecule called MTA, creating a unique weakness in cancer cells.
Researchers developed a drug called BMS-986504 that targets this weakness by selectively inhibiting the enzyme PRMT5 in MTAP-deleted cancer cells, while largely sparing normal cells. In lab and animal studies, the drug disrupted RNA processing, reduced proteins needed for cell division, and slowed tumor growth without the severe toxic effects seen with earlier drugs.
The results were strongest when the PRMT5 inhibitor was combined with KRAS-targeted therapies. This combination produced deeper and longer-lasting tumor suppression, and in some cases tumor shrinkage, suggesting a promising new clinical approach that targets two key genetic drivers of pancreatic cancer.