The awakening of an advanced malignant cancer: An insult to the mitochondrial genome
2012
Cook, Cody C. | Higuchi, Masahiro
BACKGROUND: In only months-to-years a primary cancer can progress to an advanced phenotype that is metastatic and resistant to clinical treatments. As early as the 1900s, it was discovered that the progression of a cancer to the advanced phenotype is often associated with a shift in the metabolic profile of the disease from a state of respiration to anaerobic fermentation — a phenomenon denoted as the Warburg Effect. SCOPE OF REVIEW: Reports in the literature strongly suggest that the Warburg Effect is generated as a response to a loss in the integrity of the sequence and/or copy number of the mitochondrial genome content within a cancer. MAJOR CONCLUSIONS: Multiple studies regarding the progression of cancer indicate that mutation, and/or, a flux in the copy number, of the mitochondrial genome content can support the early development of a cancer, until; the mutational load and/or the reduction-to-depletion of the copy number of the mitochondrial genome content induces the progression of the disease to an advanced phenotype. GENERAL SIGNIFICANCE: Collectively, evidence has revealed that the human cell has incorporated the mitochondrial genome content into a cellular mechanism that, when pathologically actuated, can de(un)differentiate a cancer from the parental tissue of origin into an autonomous disease that disrupts the hierarchical structure-and-function of the human body. This article is part of a Special Issue entitled: Biochemistry of Mitochondria.
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