Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


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


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} (T.W.M.); jpan{at} (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).

Read the Full Text

The Role of Nogo and the Mitochondria-Endoplasmic Reticulum Unit in Pulmonary Hypertension.
G. Sutendra, P. Dromparis, P. Wright, S. Bonnet, A. Haromy, Z. Hao, M. S. McMurtry, M. Michalak, J. E. Vance, W. C. Sessa, et al. (2011)
Science Translational Medicine 3, 88ra55
   Abstract »    Full Text »    PDF »
Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress.
K. Zaugg, Y. Yao, P. T. Reilly, K. Kannan, R. Kiarash, J. Mason, P. Huang, S. K. Sawyer, B. Fuerth, B. Faubert, et al. (2011)
Genes & Dev. 25, 1041-1051
   Abstract »    Full Text »    PDF »
Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth.
Q. Sun, X. Chen, J. Ma, H. Peng, F. Wang, X. Zha, Y. Wang, Y. Jing, H. Yang, R. Chen, et al. (2011)
PNAS 108, 4129-4134
   Abstract »    Full Text »    PDF »
HIF-1 inhibition decreases systemic vascular remodelling diseases by promoting apoptosis through a hexokinase 2-dependent mechanism.
C. M. Lambert, M. Roy, G. A. Robitaille, D. E. Richard, and S. Bonnet (2010)
Cardiovasc Res 88, 196-204
   Abstract »    Full Text »    PDF »
Phosphorylation of eIF2{alpha} at Serine 51 Is an Important Determinant of Cell Survival and Adaptation to Glucose Deficiency.
H. Muaddi, M. Majumder, P. Peidis, A. I. Papadakis, M. Holcik, D. Scheuner, R. J. Kaufman, M. Hatzoglou, and A. E. Koromilas (2010)
Mol. Biol. Cell 21, 3220-3231
   Abstract »    Full Text »    PDF »
Dysregulation of the mevalonate pathway promotes transformation.
J. W. Clendening, A. Pandyra, P. C. Boutros, S. E. Ghamrasni, F. Khosravi, G. A. Trentin, A. Martirosyan, A. Hakem, R. Hakem, I. Jurisica, et al. (2010)
PNAS 107, 15051-15056
   Abstract »    Full Text »    PDF »
Fatty Acid Oxidation and Malonyl-CoA Decarboxylase in the Vascular Remodeling of Pulmonary Hypertension.
G. Sutendra, S. Bonnet, G. Rochefort, A. Haromy, K. D. Folmes, G. D. Lopaschuk, J. R. B. Dyck, and E. D. Michelakis (2010)
Science Translational Medicine 2, 44ra58
   Abstract »    Full Text »    PDF »
Metabolic Modulation of Glioblastoma with Dichloroacetate.
E. D. Michelakis, G. Sutendra, P. Dromparis, L. Webster, A. Haromy, E. Niven, C. Maguire, T. L. Gammer, J. R. Mackey, D. Fulton, et al. (2010)
Science Translational Medicine 2, 31ra34
   Abstract »    Full Text »    PDF »
Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria.
N. Shulga, R. Wilson-Smith, and J. G. Pastorino (2010)
J. Cell Sci. 123, 894-902
   Abstract »    Full Text »    PDF »
Mitochondrial Mutations Contribute to HIF1{alpha} Accumulation via Increased Reactive Oxygen Species and Up-regulated Pyruvate Dehydrogenease Kinase 2 in Head and Neck Squamous Cell Carcinoma.
W. Sun, S. Zhou, S. S. Chang, T. McFate, A. Verma, and J. A. Califano (2009)
Clin. Cancer Res. 15, 476-484
   Abstract »    Full Text »    PDF »
Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer.
M. A. Kiebish, X. Han, H. Cheng, J. H. Chuang, and T. N. Seyfried (2008)
J. Lipid Res. 49, 2545-2556
   Abstract »    Full Text »    PDF »
Dietary Energy Restriction Modulates the Activity of AMP-Activated Protein Kinase, Akt, and Mammalian Target of Rapamycin in Mammary Carcinomas, Mammary Gland, and Liver.
W. Jiang, Z. Zhu, and H. J. Thompson (2008)
Cancer Res. 68, 5492-5499
   Abstract »    Full Text »    PDF »
Laforin Confers Cancer Resistance to Energy Deprivation-Induced Apoptosis.
Y. Wang, Y. Liu, C. Wu, B. McNally, Y. Liu, and P. Zheng (2008)
Cancer Res. 68, 4039-4044
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882