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Article Abstract

Tumor drug resistance is a crucial scientific and technological issue that urgently needs to be addressed in cancer treatment. In recent years, research on Lactate dehydrogenase A (LDHA) in the field of tumor drug resistance has progressively deepened, with breakthrough advancements achieved. Due to their metabolic characteristics, tumors often exhibit abnormal LDHA expression, which meets their growth requirements by promoting glycolysis and lactate production. A series of studies in recent years has revealed that in drug-resistant tumors, LDHA regulates its own expression through molecules such as transcription factors and non-coding RNAs, and regulates tumor drug resistance by influencing the stemness of tumor stem cells, TME, and intrinsic tumor drug resistance. In this paper, we first present timely updates on the expression and regulatory mechanisms of LDHA. Importantly, we systematically expound on the mechanisms through which LDHA is implicated in drug resistance to radiotherapy, chemotherapy, and immunotherapy in tumors, including lung and breast cancers. We also discuss a series of scientific issues that urgently need to be elucidated in future research in this field, aiming to provide more evidence and references for elucidating the mechanisms of LDHA-mediated tumor drug resistance and developing new intervention strategies against tumor drug resistance.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210585PMC
http://dx.doi.org/10.1186/s12967-025-06773-zDOI Listing

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