Hany A. Omar, Lisa Berman-Booty, Samuel K. Kulp, and Ching-Shih Chen. Energy Restriction as an Antitumor Target. Future Oncology, 2010 Nov; 6(11), 1675–1679

Research Abstract

The high need for energy in rapidly growing tumor cells links their survival to the robust availability of energy. In contrast to normal cells, transformed cells lack metabolic flexibility and switch to a glycolytic phenotype for energy production, an adaptive response to intermittent hypoxia that persists even in the presence of normal oxygen tension, the so-called Warburg effect [1–6]. This shift in energy production from oxidative phosphorylation to glycolysis is considered to be a fundamental property of cancer cells through the dysregulation of the pathways mediated by c-Myc and Akt [7–9]. This dependence on glycolysis for energy production has been linked to protection against the constitutive oxidative stress experienced by tumor cells [10–13]. The glycolytic switch can fuel the intracellular antioxidant machinery with reducing equivalents, such as NADPH, to raise tolerance to reactive oxygen species. In addition, the high rate of glycolytic flux associated with aerobic glycolysis enables tumor cells to divert intermediates of glycolysis into anabolic pathways for the synthesis of fatty acids, nucleotides and amino acids [2,4,14]. Recent evidence indicates that the glycolytic end product lactate serves as a biosynthetic intermediate for various cellular building blocks, thereby providing a growth advantage [15,16].

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