Over expression of the metabolic gene phosphoglycerate dehydrogenase (PHGDH) may trigger breast cancer, suggests a letter published in Nature. The research is seen as providing important validation for the emerging field of cancer metabolism.

Cancer metabolism is a new field in biology where profound changes in nutrient requirements and usage occur to ensure cancer cell proliferation and survival. Research has suggested that cancer cells become addicted to certain fuel sources and metabolic pathways and that identifying and disrupting different enzymes in the pathways would provide an opportunity for the discovery and development of new cancer therapies.

In the current study, which represents a joint collaboration between the Whitehead Institute (Cambridge, MA, USA) and Agios Pharmaceuticals (Cambridge, MA, USA) , investigators used a new high throughput technique called method called "RNA interference (RNAi) based loss of function screening" to investigate metabolic pathways as a potentially rich source of unexploited cancer targets. Altogether the team explored more than 133 potential metabolic targets in breast cancer cells.

Results of the screen identified several metabolic c enzymes for further follow-up including a key regulatory enzyme in the serine biosynthesis pathway. Subsequent metabolomics and metabolic flux analysis provided evidence of the mechanism whereby the serine synthesis pathway supports malignant cell growth in oestrogen-negative breast cancer.

PHGDH, a key enzyme in the serine biosynthesis pathway, is amplified in many cancers. This, say the authors, gives rise to the possibility that screening for the amplification could help to identify patients who would be candidates for therapies targeting the pathway.

"This research strongly suggests a central role for metabolic pathways in driving the growth of certain breast cancer cells. The serine pathway, and in particular the enzyme PHGDH, present a promising area for further study in the search for new therapeutic targets in cancer," says David Sabatini, the senior author of the study.

Article: R Possemato, K M Marks, Y D Shaul, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. Doi: 10.1038/nature10350.