A number of glycolytic enzymes were overexpressed in BxPC3 than in BxPC3-SMAD4+ Exo, and glycolysis was one of the core biological processes significantly altered in an SMAD4 associated manner and this allows us to add SMAD4 to the repertoire of cancer-associated genetic alterations, which include KRAS activating mutations, TP53 loss of function and MYC overexpression, which regulate the metabolic reprogramming of cancer cells, also known as the Warburg effect [47]. The gene discussed is SMAD4; the disease is cancer.