ReviewGene-to-screenTargeting amino acid metabolism for cancer therapy

- Cellular metabolism is 'reprogrammed' to support tumorigenesis.
- Amino acids fulfill many metabolic requirements of proliferating cells.
- Specific metabolic pathways can be inhibited for cancer therapy.
- Microenvironment and culture conditions significantly impact metabolic phenotype.
- Drugs targeting amino acid metabolism are now undergoing clinical evaluation.

To support sustained biomass accumulation, tumor cells undergo metabolic reprogramming. Nutrient transporters and metabolic enzymes are regulated by the same oncogenic signals that drive cell-cycle progression. Some of the earliest cancer therapies used antimetabolites to disrupt tumor metabolism, and there is now renewed interest in developing drugs that target metabolic dependencies. Many cancers exhibit increased demand for specific amino acids, and become dependent on either an exogenous supply or upregulated de novo synthesis. Strategies to exploit such 'metabolic addictions' include depleting amino acids in blood serum, blocking uptake by transporters and inhibiting biosynthetic or catabolic enzymes. Recent findings highlight the importance of using appropriate model systems and identifying target patient groups as potential therapies advance into the clinic.