{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:17:06Z","timestamp":1791472626643,"version":"4.3.4"},"reference-count":164,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MICIU\/AEI\/10.13039\/501100011033","award":["RYC2021-031003I"],"award-info":[{"award-number":["RYC2021-031003I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Oxidative and glycolytic metabolism produce energy in the form of ATP and produce intermediates for biomass production. Oxidative metabolism predominates under normoxic conditions and in quiescent or slowly proliferating cells. On the other hand, under hypoxic or pseudohypoxic conditions and in rapidly proliferating cells, glycolysis becomes the predominant pathway. The balance between oxidative and glycolytic metabolism is finely tuned in physiological conditions and becomes dysregulated in many pathological conditions, most notably cancer. In this article we summarize the evidence that has been gathered over the last few years on the mechanisms underlying this balance and the consequences of their dysregulation. We discuss first the non-metabolic factors (mitochondria, cell cycle, cell type, tissue type), then molecules that are at the intersection between glycolytic and oxidative metabolism and those molecules that are inherent to oxidative or glycolytic metabolism that affect the equilibrium between the two energy-producing pathways. Eventually, we discuss pharmacologic or genetic means that allow manipulating this equilibrium. As will be seen, lactic acidosis has taken center stage in this field and lactate has been shown to fuel oxidative metabolism. This suggests that if glycolytic metabolism predominates, as has often been shown in cancer, mechanisms come into work that reestablish a metabolic heterogeneity. Thus, while one pathway may be predominant over the other, it seems as if fail-safe mechanisms are at work that avoid the possibility that it becomes the only energy-producing pathway. Eventually, we discuss possible therapeutic consequences that may derive from this expanding knowledge, in particular, as regards tumor therapy.<\/jats:p>","DOI":"10.3390\/cells14151177","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:09:27Z","timestamp":1753891767000},"page":"1177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-4862","authenticated-orcid":false,"given":"Marco","family":"Cordani","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-7620","authenticated-orcid":false,"given":"Cristiano","family":"Rumio","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Trentacoste 2, 20134 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Bontempi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy"},{"name":"Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense, 292, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-8381","authenticated-orcid":false,"given":"Raffaele","family":"Strippoli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy"},{"name":"Gene Expression Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense, 292, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-294X","authenticated-orcid":false,"given":"Fabrizio","family":"Marcucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Trentacoste 2, 20134 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.24976\/Discov.Med.202436185.102","article-title":"The role of oxidative metabolism in tumorigenesis and drug resistance","volume":"36","author":"Marcucci","year":"2024","journal-title":"Discov. 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