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Elevated LDHA activity supports rapid ATP production under hypoxic conditions, maintains NAD+ regeneration, and promotes lactate accumulation, creating an acidic tumor microenvironment (TME) that favors invasion and immune evasion. Accumulating evidence demonstrates that LDHA is essential for primary tumor growth and critically involved in circulating tumor cell (CTC) survival, anoikis resistance, and metastatic spread. These functions are mediated by its regulation of adhesion molecules, cytoskeletal remodeling, and energy adaptation that enable CTCs to withstand mechanical shear stress and immune surveillance in the bloodstream. Pharmacological inhibition of LDHA, particularly via sodium oxamate (oxamate), has shown substantial potential in reducing metastasis and enhancing chemotherapy sensitivity in preclinical models. Oxamate has emerged as a promising candidate for metabolic cancer therapy due to its unique double effects on tumor metabolism and anti-tumor immunity, which are an advantage rarely highlighted in broader LDHA-focused reviews. This review synthesizes the molecular mechanisms through which LDHA drives tumor progression, dissects its context-specific functions in CTC biology, and evaluates the translational potential of LDHA-targeted strategies, with a focused emphasis on oxamate, as a transformative anti-metastatic therapeutic paradigm. By filling a critical gap in synthesizing oxamate\u2019s distinct metabolic\u2013immune regulatory actions, this work addresses an unmet need in the management of advanced, treatment-refractory cancers.<\/jats:p>","DOI":"10.3390\/ijms27073245","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:14:43Z","timestamp":1775142883000},"page":"3245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6349-631X","authenticated-orcid":false,"given":"Yurii V.","family":"Stepanov","sequence":"first","affiliation":[{"name":"Department of Pathophysiology of Metastasis, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8657-1263","authenticated-orcid":false,"given":"Galyna I.","family":"Solyanik","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Metastasis, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Yakshibaeva","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Metastasis, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Kolesnik","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology of Metastasis, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmyla I.","family":"Stepanova","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, 01601 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-6588","authenticated-orcid":false,"given":"Iuliia","family":"Golovynska","sequence":"additional","affiliation":[{"name":"Key Laboratory of Optoelectronic Devices and Systems, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41571-022-00686-2","article-title":"The multiple roles of LDH in cancer","volume":"19","author":"Claps","year":"2022","journal-title":"Nat. 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