It is well documented that cancers regulated three metabolic pathways to augment cancer serine content: (1) the glycolysis and glutaminolysis to provide 3-phosphoglycerate (3-PG) and glutamate, respectively, to fuel do novo serine synthesis pathways (SSP) through metabolic enzymes of PHGDH, PSAT1, and PSPH [5,59]; (2) increased take up of extracellular serine to augment intracellular serine through L-type amino acid transporter 1 (SLC7A5) [60,61]; and (3) production of serine from glycine through methyltransferases SHMT1 (cytoplasmic) and SHMT2 (mitochondrial) [62,63,64]. The gene discussed is SHMT2; the disease is cancer.