Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Gustave Roussy Cancer Campus, Villejuif, France.
Department of Radiology and Nuclear Medicine, Gustave Roussy, Villejuif, France.
Nat Rev Clin Oncol. 2022 Dec;19(12):749-762. doi: 10.1038/s41571-022-00686-2. Epub 2022 Oct 7.
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.
血清乳酸脱氢酶（LDH）水平升高通常与许多癌症类型的预后不良有关。即使是过去十年中使黑色素瘤患者的治疗效果发生重大改变的最有效的药物，对血清 LDH 水平升高的患者也只有微小的益处。从肿瘤学、生物化学、生物学和免疫学的角度分别来看，血清 LDH 的解读往往大不相同。肿瘤学家通常仅将高血清 LDH 视为预后不良的可靠生物标志物，而生物化学家长期以来一直意识到各种 LDH 同工酶的复杂性及其在癌症代谢中的关键作用，而 LDH 通常被癌症生物学家和免疫学家认为具有致癌性和/或免疫抑制性。整合这些不同的观点表明，五个 LDH 同工酶的调节及其酶和非酶功能与关键的肿瘤发生过程密切相关。在这篇综述中，我们强调血清 LDH 远不只是肿瘤负担的简单指标；它是一种复杂的生物标志物，与几种致癌信号通路的激活以及许多肿瘤的代谢活性、侵袭性和免疫原性相关，是癌症治疗的极具吸引力的靶点。
