Scientists at Johns Hopkins have identified a compound that could be used to starve cancers of their sugar-based building blocks. The compound, called a glutaminase inhibitor, has been tested on laboratory-cultured, sugar-hungry brain cancer cells and, the scientists say, may have the potential to be used for many types of primary brain tumors.
The Johns Hopkins scientists, are inventors on patent applications related to the discovery, caution that glutaminase inhibitors have not been tested in animals or humans, but their findings may spark new interest in the glutaminase pathway as a target for new therapies.
Glutaminase is an enzyme that controls how glucose-based nutrients are converted into the carbon skeleton of a cell. Additional enzymes that help construct the so-called "bricks" of the carbon skeleton are controlled by a gene called IDH1. In some brain cancer cells, IDH1 is mutated and the resulting enzyme grinds up the bricks into nutrients that feed cancer cells.
"Cancer cells with mutated IDH1 become addicted to the glutaminase pathway, and this pathway may represent an Achilles' heel of cancer cells," says Chi Dang, M.D., Ph.D., The Johns Hopkins Family Professor in Oncology Research and Vice Dean for Research at the Johns Hopkins University School of Medicine. "To combat cancer, we might block the flow of materials that help create the bricks, starting with glutaminase."
To establish proof of the principle, the Johns Hopkins scientists and a team of chemists and geneticists at Princeton University used a glutaminase-blocking agent on cells engineered to have IDH1 mutations. The compound, called BPTES, reduced growth of the cancer cells by 30 percent. Their findings were published online November 2 in Cancer Research.
"The glutaminase inhibitor we tested does not completely stop cancer cell growth, but slows it down," says Gregory Riggins, M.D., Ph.D., the Irving J. Sherman, M.D. Professo
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Johns Hopkins Medical Institutions