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http://www.nutritionandmetabolism.com/content/7/1/7

Cancer as a metabolic disease

Thomas N Seyfried email and Laura M Shelton email

Nutrition & Metabolism 2010, 7:7doi:10.1186/1743-7075-7-7
Published: 27 January 2010
Abstract (provisional)

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.

The complete article is available as a provisional PDF.

Quote:

Conclusions
Evidence is reviewed supporting a general hypothesis that cancer is primarily a disease of energy metabolism. All of the major hallmarks of the disease can be linked to impaired mitochondrial function. In order to maintain viability, tumor cells gradually transition to substrate level phosphorylation using glucose and glutamine as energy substrates. While cancer causing germline mutations are rare, the abundance of somatic genomic abnormalities found in the majority of cancers can arise as a secondary consequence of 31 mitochondrial dysfunction. Once established, somatic genomic instability can contribute to further mitochondrial defects and to the metabolic inflexibility of the tumor cells. Systemic metastasis is the predicted outcome following protracted mitochondrial damage to cells of myeloid origin. Tumor cells of myeloid origin would naturally embody the capacity to exit and enter tissues. Two major conclusions emerge from the hypothesis; first that many cancers can regress if energy intake is restricted and, second, that many cancers can be prevented if energy intake is restricted. Consequently, energy restricted diets combined with drugs targeting glucose and glutamine can provide a rational strategy for the longerterm management and prevention of most cancers.

Patrick