Although a defining mutational event in pancreatic cancer initiation is the presence of oncogenic KRAS, more advanced PDAC lesions accumulate additional genomic alterations, including loss of tumor suppressor gene TP53. Co-occurrence of mutant KRAS and TP53 in PDAC promotes hyperactivation of cancer cell signaling pathways driving epithelial to mesenchymal plasticity (EMP). The gene discussed is KRAS; the disease is pancreatic neoplasm.