Mutations in KRAS are often accompanied by secondary mutations, most commonly in tumor protein p53 (TP53, > 60% of cases), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4) genes, conferring unique advantages to PDACs in therapy resistance and tumor aggression [26, 27]. The gene discussed is SMAD4; the disease is neoplasm.