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The glycolytic switch in the progression of colorectal cancer.
Colorectal cancer is the third most common malignancy worldwide and the second cause of death in Western Europe. The prognosis and the overall survival is mainly determined by the progression of liver secondary disease rather than the primary carcinoma and if liver metastases remain untreated life expectancy is less than a year. Mitochondrial oxidative phosphorylation and cytosolic glycolysis are the two main biochemical pathways in the cell that generate adenosine triphosphate (ATP). Glycolysis converts glucose into pyruvate with the concomitant production of a relatively small amount of ATP. The reduced forms of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) formed during glycolysis and in the citric acid cycle are subsequently oxidised. The energy of these oxidation reactions is converted into ATP by oxidative phosphorylation which is the main source of ATP in aerobic cells. It has been reported that there is a switch in glucose metabolism from oxidative phosphorylation in favour of glycolysis in malignant tumours. The main aim of this project is to confirm that a glycolytic switch occurs in primary colorectal cancer and extend this observation to colorectal liver metastases. If the switch is found to be exaggerated in liver metastases, therapy that reverses this switch may not only be used for treatment of the primary tumour but will also prevent metastases from occurring.
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