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Sci. STKE, 10 April 2007
Vol. 2007, Issue 381, p. pe14
[DOI: 10.1126/stke.3812007pe14]

PERSPECTIVES

Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era?

James G. Pan1* and Tak W. Mak2*

1Campbell Family Institute for Breast Cancer Research, University Health Network TMDT East Tower, MaRs Centre, 101 College Street, 5-705, Toronto, ON M5G 1L7, Canada.
2Campbell Family Institute for Breast Cancer Research, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, ON, M5G 2C1, Canada.

Abstract: As a result of a spectrum of mitochondrial defects, tumor cells often preferentially use glycolysis to generate adenosine triphosphate (ATP), even in the presence of oxygen, a phenomenon known as aerobic glycolysis, or the "Warburg effect." Dichloroacetate (DCA) is an inhibitor of mitochondrial pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), a gatekeeping enzyme for the entry of pyruvate into the mitochondrial tricarboxylic acid (TCA) cycle. In mice, DCA treatment appears to reactivate mitochondrial respiration in tumor cells, induces their selective killing, and suppresses cancer growth. These observations provide intriguing insights into the plasticity of tumor metabolism that may offer new opportunities for therapeutic intervention.

*To whom correspondence should be addressed. E-mail: tmak{at}uhnresearch.ca (T.W.M.); jpan{at}uhnres.utoronto.ca (J.G.P.)

Citation: J. G. Pan, T. W. Mak, Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era? Sci. STKE 2007, pe14 (2007).

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