October 21, 2011
Feed A Cold — Starve A Tumor
The condition tuberous sclerosis, due to mutation in one of two tumor suppressor genes, TSC1 or TSC2, causes the growth of non-malignant tumors throughout the body and skin. These tumors can be unsightly and cause serious damage to organs. Growth of tumors in the brain may cause seizures and in the kidney, liver or heart, tumors can disrupt normal function, to the extent of causing the organ to fail. New research published in BioMed Central's open access journal Cell and Bioscience shows that the growth of glucose-dependent TSC-related tumors can be restricted by 2-deoxyglucose, which blocks glucose metabolism, but not by restricting dietary carbohydrates.
TSC1 and TSC2 normally inhibit the mTOR signaling pathway but if the TSC genes are mutated, so that they no longer function, unregulated mTORC1 drives glycolysis and cell growth. Rapamycin works by blocking mTORC1 and is currently used to treat tuberous sclerosis. However, rapamycin is an immunosuppressant and can have significant side effects, especially when used long term. A group of researchers from the University of Washington, led by Prof Yeung, looked in detail at the potential of blocking cell proliferation by directly reducing glycolysis.
Compounds such as 2DG are able to inhibit TSC2-negative tumor growth by restricting glycolysis in a manner not seen by reducing dietary glucose. 2DG is currently undergoing trials for use in prostate cancer. This and other metabolic interventions hold promise for future cancer treatment.
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