Cancer cells modify their metabolism in order to survive and grow. For example, they employ the Warburg effect (increasing glucose uptake and directly converting it to lactate) to ultimately protect against accumulation of harmful reactive oxygen species (ROS). Since many of these altered pathways are unique to cancer cells, they are hot topics for cancer research and they are new therapeutic targets for drug discovery. These include:
—Amino acid (primarily glutamine) uptake and metabolism
—Mitochondrial function, including: TCA cycle, mitochondrial DNA, Fatty acid oxidation (FAO) and Oxidative phosphorylation (OXPHOS)
—Signaling pathways such as: PI3K/AKT; HIF-1α and Myc; AMPK; NF-kB and p53; Notch
Small molecules that block (or activate) these pathways are thus great tools for cancer metabolism research. For example, CPI-613 blocks several mitochondrial pathways used by cancer cells resulting in cell death. Enasidenib is selective for mutated isocitrate dehydrogenase 2 (IDH2), which occurs in some forms of cancer. And 2-Deoxy-D-Glucose is a popular tool to block cancer cell glucose metabolism and induce apoptosis.