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The multiple roles of LDH in cancer

Nature Reviews Clinical Oncology volume 19, pages 749–762 (2022)Cite this article

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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.

Key points

  • High serum lactate dehydrogenase (LDH) levels are associated with a poor prognosis and a negative therapeutic outcome in most patients with cancer, particularly in those with melanoma.

  • The clinical role of LDH is limited to use as a prognostic serum-based biomarker associated with tumour burden; however, it also has a role in several aspects of oncogenesis.

  • LDH isoenzymes have both direct and indirect roles in many aspects of cancer progression through mechanisms such as metabolic pathway plasticity and tumour cell immune evasion.

  • LDH enzymes orchestrate various hallmarks of cancer and are thus considered highly attractive targets for cancer therapy.

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Fig. 1: Structure and function of human lactate dehydrogenase isoenzymes.
Fig. 2: Glycolysis and lactate fermentation.
Fig. 3: Regulation of LDH expression.

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Acknowledgements

The authors thank S. Bazin, O. and C. Courtin, Ensemble Contre le Mélanome, the Foundation Crédit Mutuel, Foundation Carrefour and the association Vaincre le Mélanome for their ongoing research funding support.

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Author notes

  1. These authors contributed equally: Giuseppina Claps, Sara Faouzi, Virginie Quidville.

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Gustave Roussy Cancer Campus, Villejuif, France

    Giuseppina Claps, Sara Faouzi, Virginie Quidville & Caroline Robert

  2. Department of Radiology and Nuclear Medicine, Gustave Roussy, Villejuif, France

    Feras Chehade

  3. Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China

    Shensi Shen

  4. Centre National de la Recherche Scientifique (CNRS) UMR3348 and Institut National de la Santé et de la Recherche médicale (INSERM) U1278, Curie Institute, Orsay, France

    Stéphan Vagner

  5. Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France

    Caroline Robert

  6. Faculty of Medicine, University Paris-Saclay, Kremlin Bicêtre, France

    Caroline Robert

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Contributions

G.C., S.F., V.Q. and C.R. researched data for this article, all authors made a substantial contribution to discussions of content, G.C., S.F., V.Q. and C.R. wrote the manuscript and all authors reviewed and/or edited the manuscript prior to submission.

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Correspondence to Caroline Robert.

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Competing interests

S.V. is a co-founder of Ribonexus. C.R. has acted as a consultant for Astra Zeneca, BMS, MSD, Pfizer, Pierre Fabre, Roche and Sanofi and is a co-founder of Ribonexus. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks G. Di Stefano, E. Giovannetti, Douglas Johnson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Claps, G., Faouzi, S., Quidville, V. et al. The multiple roles of LDH in cancer. Nat Rev Clin Oncol 19, 749–762 (2022). https://doi.org/10.1038/s41571-022-00686-2

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