{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:47Z","timestamp":1790751407302,"version":"4.1.0"},"reference-count":0,"publisher":"American Physiological Society","funder":[{"DOI":"10.13039\/501100001871","name":"MEC | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0050\/2020"],"award-info":[{"award-number":["LA\/P\/0050\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"EC | European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE2030-FEDER-02705300"],"award-info":[{"award-number":["NORTE2030-FEDER-02705300"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["308085\/2022-1"],"award-info":[{"award-number":["308085\/2022-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"MEC | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/06304\/2025"],"award-info":[{"award-number":["UID\/06304\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Portuguese Cancer League - North Branch","award":["LPCC-NRN 2025"],"award-info":[{"award-number":["LPCC-NRN 2025"]}]},{"name":"ICVS - Life and Health Sciences Research Institute","award":["CTTI-PI-04\/25-ICVS(1)"],"award-info":[{"award-number":["CTTI-PI-04\/25-ICVS(1)"]}]},{"name":"Portuguese Cancer League - North Branch","award":["Fellowship - LPCC-NRN 2025"],"award-info":[{"award-number":["Fellowship - LPCC-NRN 2025"]}]},{"name":"Portuguese Cancer League - North Branch","award":["Advanced Fellowship - LPCC-NRN 2026"],"award-info":[{"award-number":["Advanced Fellowship - LPCC-NRN 2026"]}]},{"name":"Centro de Investiga\u00e7\u00e3o do IPO do Porto","award":["UID\/00776\/2025; DOI: 10.54499\/UID\/00776\/2025"],"award-info":[{"award-number":["UID\/00776\/2025; DOI: 10.54499\/UID\/00776\/2025"]}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["Physiological Reviews"],"abstract":"<jats:p>Monocarboxylate transporters (MCTs) are vital to physiological pH regulation, redox balance, and energy homeostasis by mediating proton-coupled transport of lactate and other monocarboxylates across cell membranes. MCT1 and MCT4 are especially important during metabolically demanding states, where they support lactate shuttling between oxidative and glycolytic cells. To sustain rapid growth and biosynthesis, the metabolism of highly proliferative cells, including cancer cells, shifts toward glycolysis with increased lactate production. In this setting, MCTs enable lactate and proton efflux, preventing intracellular acidification and maintaining glycolytic flux. Cancer cells frequently co-opt this system, overexpressing MCT1 and MCT4, which is associated with aggressive behavior, poor prognosis, and treatment resistance. These insights have motivated the development of MCT inhibitors, one of which has entered early clinical evaluation, suggesting potential therapeutic benefit in selected tumors. This review first introduces core aspects of cellular metabolism and then outlines the physiological roles, regulation, and tissue distribution of MCTs in normal tissues. It next examines how MCTs are dysregulated across cancer types to support the glycolytic phenotype, remodel the tumor microenvironment, and drive malignant progression, with particular focus on the prognostic impact of MCT expression. The article summarizes evidence linking MCT overexpression to poor outcomes and therapy resistance, and surveys efforts to therapeutically target MCTs and key translational barriers. Finally, it highlights future directions for exploiting MCT biology in precision oncology.<\/jats:p>","DOI":"10.1152\/physrev.00004.2026","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:47:56Z","timestamp":1790707676000},"update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Monocarboxylate Transporters (MCTs) in Physiology and Cancer: from Fundamentals to Clinical Translation"],"prefix":"10.1152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9748-3752","authenticated-orcid":false,"given":"Julieta","family":"Afonso","sequence":"first","affiliation":[{"name":"University of Minho"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Pereira-Vieira","sequence":"additional","affiliation":[{"name":"University of Minho"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Miranda-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute of Porto (IPO Porto)"},{"name":"RISE Associate Laboratory (Health Research Network)"},{"name":"Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca)"},{"name":"University of Porto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Granja","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico do Porto"},{"name":"Department of Pathological"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Barretos Cancer Hospital"},{"name":"Barretos School of Health Sciences Dr. Paulo Prata - FACISB"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-4544","authenticated-orcid":false,"given":"F\u00e1tima","family":"Baltazar","sequence":"additional","affiliation":[{"name":"University of Minho"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2026,9,29]]},"container-title":["Physiological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/physrev.00004.2026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:09:27Z","timestamp":1790748567000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/physrev.00004.2026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":0,"alternative-id":["10.1152\/physrev.00004.2026"],"URL":"https:\/\/doi.org\/10.1152\/physrev.00004.2026","relation":{},"ISSN":["0031-9333","1522-1210"],"issn-type":[{"value":"0031-9333","type":"print"},{"value":"1522-1210","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"physrev.00004.2026"}}