An independent study recently published in the journal Nature by the Whitehead Institute and Agios scientists also concluded that the serine pathway may play an important role in certain breast cancers. The new findings were generated using a novel research method called metabolic flux analysis, which may have broad application in cancer metabolism research for identification of new cancer targets.
Dr. Cantley, an Agios founder and distinguished scientific advisor, is director of the Cancer Center at Beth Israel Deaconess Medical Center and professor of systems biology at Harvard Medical School. Dr. Vander Heiden, also an advisor to Agios, is an assistant professor in the Koch Institute for Integrative Cancer Research and the Department of Biology at the Massachusetts Institute of Technology.
“This exciting new research illustrates that metabolic flux analysis, a key component of Agios’s cancer metabolism research platform, can be used to identify unique metabolic features of cancer cells, leading to the discovery of new therapeutic targets in cancer,” said David Schenkein, M.D., chief executive officer of Agios. “These recent publications underscore the promise of cancer metabolism to lead to the development of novel medicines for cancer patients. We look forward to continuing to advance the science in this potentially transformative area of drug development.”
In the research, metabolic flux analysis of cancer cell lines demonstrated that amplification of a metabolic enzyme, phosphoglycerate dehydrogenase (PHGDH), diverts glycolytic intermediates into the serine biosynthesis pathway, which may contribute to tumor formation and development. Researchers then demonstrated that knock-down of PHGDH inhibited the growth of melanoma, breast cancer and esophageal squamous cell carcinoma lines in vitro. Importantly, the Nature Genetics manuscript provides the first clear evidence that inappropriate overexpression of a single normal metabolic enzyme can cause cell transformation.
The paper, titled “Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis” was made available on Sunday, July 31, in the advanced online publication of Nature Genetics. See below for more information.