Abstract
Prominent features of cancer cells include metabolic imbalances and enhanced resistance to mitochondrial apoptosis. The fact that tumors rely heavily on glycolysis to meet their metabolic demands has been recognized since the beginning of the twentieth century, yet a complete elucidation of the so-called Warburg effect has not been achieved. Several mechanisms have been proposed to explain this phenomenon, including the upregulation of rate-limiting steps of glycolysis, the accumulation of mutations in the mitochondrial genome, the hypoxia-induced switch from mitochondrial respiration to glycolysis or the metabolic reprogramming resulting from the loss-of-function of enzymes like fumarate and succinate dehydrogenases. How aerobic glycolysis and apoptosis resistance are linked remains to be elucidated. On the one hand, these alterations may be acquired independently by cancer cells during multistep oncogenesis. On the other hand, the suppression of the intrinsic apoptotic program may be achieved through mechanisms that directly lead to the Warburg phenotype. Cancer-specific mitochondrial alterations and bioenergetics may be taken advantage for the development of two novel classes of antineoplastic agents. A first approach would target glycolysis and/or revert the Warburg phenomenon, whereas a second approach would aim at inducing apoptosis by targeting mitochondrial proteins and membranes. In both instances, encouraging pre-clinical results have been obtained.
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References
Alirol E, Martinou JC . (2006). Oncogene, in press, this issue.
Brandon M, Baldi P, Wallace DC . (2006). Oncogene, in press, this issue.
Brenner C, Grimm S . (2006). Oncogene, in press, this issue.
Cereghetti GM, Scorrano L . (2006). Oncogene, in press, this issue.
Chatterjee A, Mambo E, Sidransky D . (2006). Oncogene, in press, this issue.
Cheng WC, Berman SB, Jonas EA, Lee SJ, Chen Y, Pineda F et al. (2006). Oncogene, in press, this issue.
Debatin KM, Poncet D, Kroemer G . (2002). Oncogene 21: 8786–8803.
Fantin VR, Leder P . (2006). Oncogene, in press, this issue.
Fontenay M, Cathelin S, Amiot M, Gyan E, Solary E . (2006). Oncogene, in press, this issue.
Fulda S, Debatin KM . (2006). Oncogene, in press.
Galluzzi L, Larochette N, Zamzami N, Kroemer G . (2006). Oncogene, in press, this issue.
Green DR, Kroemer G . (2004). Science 305: 626–629.
King A, Selak MA, Gottlieb E . (2006). Oncogene, in press, this issue.
Mathupala SP, Ko YH, Pedersen PL . (2006). Oncogene, in press, this issue.
Moll UM, Marchenko N, Zhang XK . (2006). Oncogene, in press, this issue.
Ohta S . (2006). Oncogene, in press, this issue.
Pelicano H, Martin DS, Xu RH, Huang P . (2006). Oncogene, in press, this issue.
Robey RB, Hay N . (2006). Oncogene, in press, this issue.
Warburg O . (1930). The metabolism of tumours. Constable: London.
Zamzami N, Brenner C, Marzo I, Susin SA, Kroemer G . (1998). Oncogene 16: 2265–2282.
Zhivotovsky B, Kroemer G . (2004). Nat Rev Mol Cell Biol 117: 4461–4468.
Acknowledgements
The author's own work is supported by a special grant of the Ligue Nationale contre le Cancer, as well as by grants from the European Union (Active p53, RIGHT, Trans-Death).
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Kroemer, G. Mitochondria in cancer. Oncogene 25, 4630–4632 (2006). https://doi.org/10.1038/sj.onc.1209589
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DOI: https://doi.org/10.1038/sj.onc.1209589
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