The multiple roles of LDH in cancer
Abstract
High serum lactate dehydrogenase (LDH) levels are typically associated with a poor prognosis in many cancer types. Even the most effective drugs, which have radically improved outcomes in patients with melanoma over the past decade, provide only marginal benefit to those with high serum LDH levels. When viewed separately from the oncological, biochemical, biological and immunological perspectives, serum LDH is often interpreted in very different ways. Oncologists usually see high serum LDH only as a robust biomarker of a poor prognosis, and biochemists are aware of the complexity of the various LDH isoforms and of their key roles in cancer metabolism, whereas LDH is typically considered to be oncogenic and/or immunosuppressive by cancer biologists and immunologists. Integrating these various viewpoints shows that the regulation of the five LDH isoforms, and their enzymatic and non-enzymatic functions is closely related to key oncological processes. In this Review, we highlight that serum LDH is far more than a simple indicator of tumour burden; it is a complex biomarker associated with the activation of several oncogenic signalling pathways as well as with the metabolic activity, invasiveness and immunogenicity of many tumours, and constitutes an extremely attractive target for cancer therapy.
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LDH catalyzes the bidirectional conversion of pyruvate and lactate, with LDHA having a higher affinity for pyruvate and LDHB a higher affinity for lactate.
“LDH catalyzes the bidirectional conversion of pyruvate and lactate, with LDHA reportedly having a higher affinity for pyruvate (Claps et al., 2022;Mishra & Banerjee, 2019) and LDHB a higher affinity for lactate (Kopperschläger & Kirchberger, 1996;Read et al., 2001).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Claps et al., 2022
Because LDH tetramers with a surplus of LDHA subunits are biased toward lactate generation, findings argue that immature oligodendrocytes produce and release lactate during development and remyelination.
“Since LDH tetramers with a surplus of LDHA subunits are biased toward the generation of lactate (Claps et al., 2022;Mishra & Banerjee, 2019) these findings rather argue in favor of the production and release of lactate from immature oligodendrocytes under these conditions.”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Claps et al., 2022
Cites
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Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma
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Self-citationMetabolic plasticity underpins innate and acquired resistance to LDHA inhibition
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Späte, E., Zhou, B., Sun, T., Kusch, K., Asadollahi, E., Siems, S. B., Depp, C., Werner, H. B., Saher, G., Hirrlinger, J., et al. (2024) · Glia · doi:10.1002/glia.24533 · Cited by 40 · see citing works
The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities
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- Authors
- Claps, G., Faouzi, S., Quidville, V., Chehade, F., Shen, S., Vagner, S., & Robert, C.
- Affiliations
- Inserm (FR)
- Sichuan University (CN)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Robert, Caroline
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2022-10-07
- Volume
- 19
- Issue
- 12
- Pages
- 749-762
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W4303446545
- Cited by
- 351
- References
- 6
- Citations by year
- 2026: 101 · 2025: 126 · 2024: 77 · 2023: 45 · 2022: 1
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- lactate dehydrogenase, serum lactate dehydrogenase, cancer prognosis, cancer metabolism, tumor immunosuppression, tumor immunogenicity, oncogenic signalling pathways, tumour invasiveness, prognostic factors
- MeSH terms
- Humans, L-Lactate Dehydrogenase, Melanoma, Prognosis, Tumor Burden
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