Clinical impact of the Warburg effect in gastrointestinal cancer (review).

Abstract

Cancer cells exhibit altered glucose metabolism, termed the Warburg effect, which is described by the increased uptake of glucose and the conversion of glucose to lactate in cancer cells under adequate oxygen tension. Recent genetic and metabolic analyses have provided insights into the molecular mechanisms of genes that are involved in the Warburg effect and tumorigenesis. The aim of this review was to discuss significant molecular insights into clinical impacts of the Warburg effect such as oncogenic alterations and overexpression of transcriptional factors (c-Myc and hypoxia-inducible factor), metabolite transporters (glucose transporters) and glycolytic enzymes (hexokinases 2, pyruvate kinase M2, pyruvate dehydrogenase kinase, isozyme 1, lactate dehydrogenaseA). Overexpression of transcriptional factors, metabolite transporters and glycolytic enzymes was associated with poor prognosis and may be associated with chemoradiotherapy resistance in multiple gastrointestinal cancer cell types. Novel small molecules targeting these enzymes or transporters exert anti-proliferative effects. Glycolytic enzymes and metabolite transporters may be significant biomarkers for predicting cancer prognosis and may be therapeutic targets in gastrointestinal cancer.