Combining KRAS Inhibition and Immunotherapy: A Breakthrough for PDAC

This study demonstrates the transformative potential of combining KRAS* inhibition with immune-modulating therapies in pancreatic ductal adenocarcinoma (PDAC), a cancer notoriously resistant to conventional treatments. Researchers used a synergistic approach targeting key immune pathways with a CXCR1/2 inhibitor, anti-LAG3 antibody, and anti-41BB antibody in a genetically engineered PDAC mouse model. This combination not only suppressed tumor growth but achieved complete and durable regressions in 36% of cases, with mice surviving up to 6 months. Mechanistic analyses revealed enhanced T-cell activation, reduced immunosuppressive myeloid cells, and increased dendritic cell-mediated antigen presentation. These findings provide compelling evidence for integrating KRAS* inhibitors with immunotherapy to overcome PDAC’s immune evasion, paving the way for clinical trials.