Researchers at the University of Texas Southwestern Medical Center have discovered genetic pathways to selectively starve kidney cancer cells. Two separate studies indicate that both rare and common cases of kidney cancer may be susceptible to a new class of drugs that inhibits cancer cells from generating the energy needed to survive. In one study, available online and scheduled for the May 5 issue of the journal Oncogene, researchers found that inactivating the gene von Hippel-Lindau (VHL) in mice blocked cells from using oxygen to provide energy to the cell, forcing them to use another method of energy generation, namely glycolysis – the conversion of glucose to lactic acid. Because the VHL gene is inactive in about 90 percent of clear-cell renal cell carcinomas, the most common type of kidney cancer in humans, the study provides a rationale for the evaluation of glycolytic inhibitors in fighting kidney cancer, said Dr. James Brugarolas, assistant professor of internal medicine and developmental biology and the study's senior author. "It would be expected to kill cancer cells preferentially and spare most normal cells that would still have mitochondrial respiration to rely on," said Dr. Brugarolas. An estimated 58,000 new cases of kidney cancer were reported in the U.S. in 2010, and 13,040 died of the disease. Based on incidence of this cancer from 2005 to 2007, 1 in 67 people will be diagnosed with cancer of the kidney or renal pelvis during his or her lifetime. The study also revealed that the effect of VHL loss was mediated by hypoxia-inducible factors (HIF), a family of proteins that binds to specific DNA sequences and responds to decreases in oxygen, known as hypoxia. "We discovered that simultaneous inactivation of HIF rescued the mice from the effects of VHL inactivation," Dr. Brugarolas said.
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