Cancer as a metabolic disease

Abstract

Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.

Figure 1

Activation of the retrograde response (RTG) response in yeast cells. The circled Ps are phosphate groups. SLP, (substrate level phosphorylation). See text for description of the RTG response.

Figure 2

Linking the hallmarks of cancer to impaired energy metabolism. See text for discussion. SLP and OxPhos represent substrate level phosphorylation and oxidative phosphorylation, respectively. The progressive damage to mitochondria during carcinogenesis is illustrated with a change in shape.