LDHA

Lactate dehydrogenase A (LDHA) catalyzes the reversible conversion of pyruvate to lactate, facilitating glycolytic energy production^[1][2]. Mechanistically, LDHA is upregulated under hypoxic conditions, driving aerobic glycolysis and supporting cellular proliferation in multiple cancer types^[3][4]. Compared with LDHB, LDHA-dominant isoforms exhibit higher expression in tumor tissues and contribute preferentially to lactate accumulation and the Warburg effect^[3][1]. LDHA has been identified as a critical modulator of tumor metabolism, influencing glucose uptake, lactate production, and mitochondrial function under energy stress conditions^[5][4]. In disease models, overexpression of LDHA promotes proliferation and migration in vitro and tumor growth in vivo, while its knockdown sensitizes cells to radiation or metabolic stress^[6][7][1]. Functionally distinct from LDHB, LDHA also participates in non-metabolic roles such as DNA repair via nuclear translocation in response to ionizing radiation, independent of glycolysis^[1]. Agonists are less studied, but small-molecule inhibitors, including N-hydroxyindole derivatives and sodium oxamate, competitively target LDHA activity, reduce lactate production, and suppress cancer cell viability, particularly under hypoxia^[2][8]. Collectively, these properties establish LDHA as both a biomarker of aggressive cancer phenotypes and a promising therapeutic target for metabolic and combination therapies^[4][7].