The principal oncogenic drivers in PAAD pathogenesis include KRAS, CDKN2A, TP53, and SMAD4. While KRAS and CDKN2A mutations typically arise during tumor initiation, aberrations in TP53 and SMAD4 are associated with disease progression and malignant transformation [38]. The gene discussed is SMAD4; the disease is pancreatic adenocarcinoma.