KRAS Mutations: A Key to Understanding Pancreatic Cancer Outcomes

This study sheds light on the clinical and biological distinctions between specific KRAS mutations in pancreatic ductal adenocarcinoma (PDAC). Analyzing 1,360 PDAC cases, researchers found that KRASG12R mutations are more prevalent in early-stage (stage I) disease and are linked to reduced nodal involvement, lower distant recurrence rates, and improved overall survival compared to KRASG12D mutations. Spatial and transcriptomic profiling revealed enhanced oncogenic and epithelial-mesenchymal transition (EMT) signaling in KRASG12D tumors, while KRASG12R tumors showed increased NF-κB signaling but decreased migration and aggressiveness in mouse models. These findings underscore the prognostic value of KRAS mutational analysis, suggesting that KRAS mutations drive distinct tumor biology and clinical trajectories, which could inform personalized treatment strategies in PDAC.