{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:33:11Z","timestamp":1792510391766,"version":"4.5.0"},"reference-count":215,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:00:00Z","timestamp":1604361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish government and the EU","award":["(FIS PI18\/00441)."],"award-info":[{"award-number":["(FIS PI18\/00441)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer is a complex disease that includes the reprogramming of metabolic pathways by malignant proliferating cells, including those affecting the tumor microenvironment (TME). The \u201cTME concept\u201d was introduced in recognition of the roles played by factors other than tumor cells in cancer progression. In response to the hypoxic or semi-hypoxic characteristic of the TME, cancer cells generate a large amount of lactate via the metabolism of glucose and glutamine. Export of this newly generated lactate by the tumor cells together with H+ prevents intracellular acidification but acidifies the TME. In recent years, the importance of lactate and acidosis in carcinogenesis has gained increasing attention, including the role of lactate as a tumor-promoting metabolite. Here we review the existing literature on lactate metabolism in tumor cells and the ability of extracellular lactate to direct the metabolic reprogramming of those cells. Studies demonstrating the roles of lactate in biological processes that drive or sustain carcinogenesis (tumor promotion, angiogenesis, metastasis and tumor resistance) and lactate\u2019s role as an immunosuppressor that contributes to tumor evasion are also considered. Finally, we consider recent therapeutic efforts using available drugs directed at and interfering with lactate production and transport in cancer treatment.<\/jats:p>","DOI":"10.3390\/cancers12113244","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T20:46:52Z","timestamp":1604436412000},"page":"3244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":394,"title":["Lactate in the Tumor Microenvironment: An Essential Molecule in Cancer Progression and Treatment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3226-1240","authenticated-orcid":false,"given":"Ricardo","family":"P\u00e9rez-Tom\u00e1s","sequence":"first","affiliation":[{"name":"Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, University of Barcelona, C.\/ Feixa Llarga s\/n, L\u2019 Hospitalet de Llobregat, 08905 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"P\u00e9rez-Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Microbiology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, University of Barcelona, C.\/ Feixa Llarga s\/n, L\u2019 Hospitalet de Llobregat, 08905 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/S0140-6736(05)60805-7","article-title":"The Nobel Chronicles. 1922: Archilbald Vivian Hill (1886-1977), Otto Fritz Meyerfhoff (1884-1951)","volume":"352","author":"Raju","year":"1998","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4065\/74.1.67","article-title":"Otto Meyerhoff--Nobel Prize for studies of muscle metabolism","volume":"74","author":"Shampo","year":"1999","journal-title":"Mayo Clin. 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