PDAC Models with KRASG12R Show Elevated MHC Class I Expression

Pancreatic cancer, the third leading cause of cancer-related deaths in the United States, carries a dismal 5-year survival rate of ~13%. Oncogenic KRAS mutations drive >90% of pancreatic ductal adenocarcinoma cases, with KRASG12D, KRASG12V, and KRASG12R predominating. Canonical KRASG12D strongly activates PI3K-AKT signaling via direct p110α binding, which represses MHC class I (MHC-I) expression and antigen presentation. In contrast, atypical KRASG12R exhibits structural disruption in its Switch