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

Abstract

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.

Keywords:

• Cancer
• anaerobic metabolism
• glycolysis
• LDHA
• LDH5
• radiotherapy
• prognosis

Disclosure statement

The authors report no conflicts of interest.

Additional information

Notes on contributors

Michael I. Koukourakis

Michael I. Koukourakis is Professor of Radiation Oncology and Head of the Department of Radiation Oncology and the Radiopathology/Radiobiology Unit at the Democritus University of Thrace, Alexandroupolis, Greece. https://www.radiotheroncolbiol-duth.gr/.

Alexandra Giatromanolaki

Alexandra Giatromanolaki is Professor of Pathology and Head of the Department of Pathology at the Democritus University of Thrace, Alexandroupolis, Greece. http://www.med.duth.gr/department/members/Giatromanolaki-eng.pdf.