The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

The pentose phosphate pathway, one of the main antioxidant cellular defense systems, has been related for a long time almost exclusively to its role as a provider of reducing power and ribose phosphate to the cell. In addition to this “traditional” correlation, in the past years multiple roles have emerged for this metabolic cascade, involving the cell cycle, apoptosis, differentiation, motility, angiogenesis, and the response to anti-tumor therapy. These findings make the pentose phosphate pathway a very interesting target in tumor cells. This review summarizes the latest discoveries relating the activity of the pentose phosphate pathway to various aspects of tumor metabolism, such as cell proliferation and death, tissue invasion, angiogenesis, and resistance to therapy, and discusses the possibility that drugs modulating the pathway could be used as potential tools in tumor therapy. The pentose phosphate pathway produces metabolites and cofactors necessary for the synthesis of GSH, lipids and ATP, for the maintenance of the glycolytic flux, for detoxification processes, for DNA duplication. Determining proliferation, apoptosis escape, invasion, angiogenesis, response to therapy, this pathway can be considered at the crossroad of tumor cell fate. [Display omitted] ► The pentose phosphate pathway (PPP) is one of the main antioxidant defenses. ► The PPP supplies cells with NADPH, ribose 5-phosphate, and glycolytic intermediates. ► In tumors the PPP sustains malignant transformation and modulates response to therapy. ► Cancer cells with high PPP flux have a more invasive and drug-resistant phenotype. ► Designing more selective pharmacological modulators of the PPP is mandatory.