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UT Southwestern research advances fight against kidney cancer
Date:3/30/2011

ing HIF is sufficient to block cells from using oxygen. It also indicates that there are no other pathways that can allow the use of available oxygen when HIF is active."

In a related study, Dr. Brugarolas examined the effectiveness of a specific glycolytic inhibitor, 2-deoxy-D-glucose (2DG), in treating a rare form of kidney cancer. The case study, available in the March 1 issue of Nature Reviews Urology, details efforts to develop a personalized treatment plan for a patient who presented with an uncommon kidney cancer type when she was 24. Without any familial predisposition for kidney or other cancers, the patient was found to have a mutation in a gene called fumarate hydratase, which has been found to be mutated in approximately 100 families worldwide and which confers a strong predisposition to kidney cancer. The mutation was a novel mutation, and the patient is likely to have been the founder, Dr. Brugarolas said.

The gene encodes an enzyme which is important for cells to be able to use oxygen and generate energy, and studies showed that the enzyme was completely inactive in the tumor. The patient, who had an advanced case of cancer, underwent surgery and then standard treatment with mTORC1 inhibitors. After five months, however, her tumor progressed and there were no other proven treatments available. Given this situation, Dr. Brugarolas looked for options to exploit what was known about the tumor. After a discussion with the UT Southwestern Institutional Review Board, the Food and Drug Administration and the drug manufacturer, Dr. Brugarolas managed to secure for his patient a drug in development, 2DG, which previously had been used only in clinical trials.

Because the tumor was deficient in fumarate hydratase, researchers speculated that 2DG would block glycolysis and kill tumor cells, as it had in the laboratory. The drug, however, failed to produce the same results for the patient, who later died. The patient had given p
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Contact: Debbie Bolles
debbie.bolles@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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