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Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment

Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 675 Hoes Lane West, Research Towers, Room 561, Piscataway, NJ 08854, USA
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Cancers 2019, 11(6), 750; https://doi.org/10.3390/cancers11060750
Received: 23 April 2019 / Revised: 20 May 2019 / Accepted: 23 May 2019 / Published: 29 May 2019
Cancer is a metabolic disease in which abnormally proliferating cancer cells rewire metabolic pathways in the tumor microenvironment (TME). Molecular reprogramming in the TME helps cancer cells to fulfill elevated metabolic demands for bioenergetics and cellular biosynthesis. One of the ways through which cancer cell achieve this is by regulating the expression of metabolic enzymes. Lactate dehydrogenase (LDH) is the primary metabolic enzyme that converts pyruvate to lactate and vice versa. LDH also plays a significant role in regulating nutrient exchange between tumor and stroma. Thus, targeting human lactate dehydrogenase for treating advanced carcinomas may be of benefit. LDHA and LDHB, two isoenzymes of LDH, participate in tumor stroma metabolic interaction and exchange of metabolic fuel and thus could serve as potential anticancer drug targets. This article reviews recent research discussing the roles of lactate dehydrogenase in cancer metabolism. As molecular regulation of LDHA and LDHB in different cancer remains obscure, we also review signaling pathways regulating LDHA and LDHB expression. We highlight on the role of small molecule inhibitors in targeting LDH activity and we emphasize the development of safer and more effective LDH inhibitors. We trust that this review will also generate interest in designing combination therapies based on LDH inhibition, with LDHA being targeted in tumors and LDHB in stromal cells for better treatment outcome. View Full-Text
Keywords: lactate dehydrogenase; LDHA; LDHB; isoenzymes; metabolism; tumor microenvironment; metabolic cooperation; tumor stroma; lactate; combination therapy lactate dehydrogenase; LDHA; LDHB; isoenzymes; metabolism; tumor microenvironment; metabolic cooperation; tumor stroma; lactate; combination therapy
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MDPI and ACS Style

Mishra, D.; Banerjee, D. Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment. Cancers 2019, 11, 750.

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