Warburg effect, lactate dehydrogenase, and radio/chemo-therapy efficacy

The anaerobic metabolism of glucose by cancer cells, even under well-oxygenated conditions, has been documented by Otto Warburg as early as 1927. Micro-environmental hypoxia and intracellular pathways activating the hypoxia-related gene response, shift cancer cell metabolism to anaerobic pathways. In the current review, we focus on a major enzyme involved in anaerobic transformation of pyruvate to lactate, namely lactate dehydrogenase 5 (LDH5). The value of LDH5 as a marker of prognosis of cancer patients, as a predictor of response to radiotherapy (RT) and chemotherapy and, finally, as a major target for cancer treatment and radio-sensitization is reported and discussed. Clinical, translational and experimental data supporting the uniqueness of the LDHA gene and its product LDH5 isoenzyme are summarized and future directions for a metabolic treatment of cancer are highlighted.