MIT & Whitehead Researchers ID Metabolic Weakness in Subset of Glioblastoma Cells; May Be New Therapeutic Target

Biologists at MIT and the Whitehead Institute for Biomedical Research have discovered a vulnerability of brain cancer cells that could be exploited to develop more-effective drugs against brain tumors. The study, led by researchers from the Whitehead Institute and MIT’s Koch Institute for Integrative Cancer Research, found that a subset of glioblastoma tumor cells is dependent on a particular enzyme (glycine decarboxylase, GLDC) that breaks down the amino acid glycine. Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. Blocking this enzyme in glioblastoma cells could offer a new way to combat such tumors, says Dr. Dohoon Kim, a postdoc at the Whitehead Institute and lead author of the study, which was published online on April 8, 2015 in Nature. Dr. David Sabatini, a Professor of Biology at MIT and member of the Whitehead Institute, is the paper’s senior author. Dr. Matthew Vander Heiden, the Eisen and Chang Career Development Associate Professor of Biology and a member of the Koch Institute, also contributed to the research, along with members of his lab. GLDC caught the researchers’ attention as they investigated diseases known as “inborn errors of metabolism,” which occur when cells are missing certain metabolic enzymes. Many of these disorders specifically affect brain development; the most common of these is phenylketonuria, marked by an inability to break down the amino acid phenylalanine. Such patients must avoid eating phenylalanine to prevent problems such as intellectual disability and seizures. Loss of GLDC produces a disorder called nonketotic hyperglycinemia, which causes glycine to build up in the brain and can lead to severe mental retardation. GLDC is also often overactive in certain cells of glioblastoma, the most common and most aggressive type of brain tumor found in humans.
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