{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:18:52Z","timestamp":1788355132579,"version":"build-2803163510"},"reference-count":176,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>As considered as a mere waste product historically, the biological functions of lactate have been overlooked for a long time. Over the past decades, accumulated data has implicated the multiple and substantial roles of lactate in physiological and pathological contexts, particularly in cancer. This review aims to provide a comprehensive overview about lactate biology in both health homeostasis and oncology. We first presented a systematic elaboration about lactate metabolism, including its property, production, transport, shuttling as well as sensing. Additionally, the multifaceted functions of lactate in tumor microenvironment were summarized to explore the underlying mechanisms during metabolic reprogramming, signaling molecule, immune modulation and epigenetic regulation. Furthermore, we assessed the current lactate-targeted strategies for cancer intervention, exploring the feasibility as therapeutic targets in clinical application. Finally, the unsolved challenges were outlined to propose illuminating directions for future investigations and accelerate its translation into clinical practice in this field.<\/jats:p>","DOI":"10.3389\/fphar.2026.1881938","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:37:13Z","timestamp":1788352633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The multifaceted functions of lactate and its translational potentials in cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Yantaishan Hospital Affiliated to Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Cardiology, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Pharmacology, Institute of Aging Medicine, Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxia","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory & Health Service Training, Shandong Medical and Pharmaceutical University Affiliated 970 Hospital of the PLA Joint Logistic Support Force","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Shandong Medical and Pharmaceutical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.3390\/biom15071010","article-title":"Context matters: divergent roles of exercise-induced and tumor-derived lactate in cancer","volume":"15","author":"Ahmadi Hekmatikar","year":"2025","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.cmet.2016.12.018","article-title":"Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments","volume":"25","author":"Angelin","year":"2017","journal-title":"Cell Metab."},{"key":"B3","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.it.2022.10.005","article-title":"Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment","volume":"43","author":"Apostolova","year":"2022","journal-title":"Trends Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12964-020-0530-4","article-title":"Tumor microenvironment complexity and therapeutic implications at a glance","volume":"18","author":"Baghban","year":"2020","journal-title":"Cell Commun. 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