The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor.
There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non-neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic.
Cellular & Molecular Neuro-oncology Research Group, University of Portsmouth, School of Pharmacy & Biomedical Sciences, Portsmouth, UK.
Cara J
http://orcid.org/0000-0001-9108-3427
CJ
Valvona
Cellular & Molecular Neuro-oncology Research Group, University of Portsmouth, School of Pharmacy & Biomedical Sciences, Portsmouth, UK.
Helen L
HL
Fillmore
Cellular & Molecular Neuro-oncology Research Group, University of Portsmouth, School of Pharmacy & Biomedical Sciences, Portsmouth, UK.
Peter B
PB
Nunn
Cellular & Molecular Neuro-oncology Research Group, University of Portsmouth, School of Pharmacy & Biomedical Sciences, Portsmouth, UK.
Geoffrey J
GJ
Pilkington
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D000080864:Lactate Dehydrogenase 5
D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
LDHA; Warburg; aerobic glycolysis; brain tumor; lactate; therapeutic target; tumor metabolism