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Cited by 277Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

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

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Mishra, Deepshikha, Banerjee, Debabrata·2019·Cancers
DOI 10.3390/cancers11060750PMC PMC6627402
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Abstract

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.

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Cited by

Sorted by citations

Authors
Mishra, D., & Banerjee, D.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
  • Mishra, Deepshikha
  • Banerjee, Debabrata
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2019-05-29
Volume
11
Issue
6
Pages
750
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers11060750
PMC
PMC6627402
OpenAlex
W2947550210
Cited by
277
References
10
Citations by year
2026: 20 · 2025: 37 · 2024: 35 · 2023: 52 · 2022: 36 · 2021: 62 · 2020: 32 · 2019: 3
FWCI
3.19
Type
journal article
Language
en
Update notices
correction (2019-05-29)
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords
lactate dehydrogenase, LDHA, LDHB, tumor microenvironment, cancer metabolism, metabolic reprogramming, signaling pathways, combination therapy, anticancer drug targets

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