How cancer cells thrive under conditions of low oxygen, or hypoxia, within tumors is poorly understood, but researchers at the OSUCCC – James have identified a mechanism that enables cancer cells to proliferate even in low oxygen. The findings might offer a new strategy for inhibiting tumor growth by reversing this hypoxia-triggered pathway. The study found that cancer cells can alter how they use the amino acid glutamine. Normally, cells use glutamine mainly to produce energy, diverting a small amount to make fatty acids and lipids. But in a growing tumor, low oxygen activates the gene HIF1, which shifts glutamine use heavily toward producing lipids needed for cell proliferation. “We have blocked the growth of model tumors by redirecting hypoxic glutamine metabolism to make it follow the normal-oxygen pathway,” says principal investigator Nicholas Denko, PhD, MD, associate professor of Radiation Oncology and member of the OSUCCC – James Molecular Biology and Cancer Genetics Program. “Such a therapeutic strategy should have few unwanted side effects because normal, oxygenated tissue is already using glutamine in the normal manner,” Denko says.