{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:06:36Z","timestamp":1791745596870,"version":"4.3.4"},"reference-count":248,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technology, and Innovation (MINCIENCIAS)","award":["653 of 2021"],"award-info":[{"award-number":["653 of 2021"]}]},{"name":"Universidad del Sin\u00fa (UNISINU)","award":["653 of 2021"],"award-info":[{"award-number":["653 of 2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer (PCa) therapy faces challenges due to tumor heterogeneity, plasticity, and progression. Metabolic reprogramming, a dynamic process, has emerged as a key focus in PCa treatment. However, conventional therapies targeting cancer-specific metabolic pathways or employing chemosensitizers are often limited by compensatory mechanisms and metabolic complexity. This review highlights the roles of transcription factors, including AR, p53, c-Myc, HIF-1, Nrf2, and PPAR\u03b3, in regulating PCa metabolism by influencing signaling pathways, enzymes, and gene expression. Multi-target compounds, particularly natural products, show potential for disrupting multiple metabolic enzymes, opening up new research possibilities. Notable examples include \u03b2-elemene, juglone, tannic acid, and withaferin A, which target critical metabolic processes through enzyme inhibition, transcription factor modulation, epigenetic changes, and protein interaction disruption. Naturally derived metabolites can elicit transversal responses in diverse metabolic pathways, particularly in p53 and MYC transcription factors. Additionally, compounds such as pentacyclic terpenoids (ursolic acid with ursane skeleton), sulforaphane, and isothiocyanate-related moieties may induce metabolic and epigenetic changes through S-adenosyl methionine (SAM) and acetyl-CoA modulation, potentially affecting new areas of research through metabolic processes. We propose a cooperative crosstalk between metabolic reprogramming and transcription factors\/epigenetic modulation in PCa. This approach holds potential for expanding PCa therapeutics and opening new avenues for research.<\/jats:p>","DOI":"10.3390\/ijms26136013","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T09:08:44Z","timestamp":1750669724000},"page":"6013","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-9967","authenticated-orcid":false,"given":"Pedro Juan","family":"Espitia-P\u00e9rez","sequence":"first","affiliation":[{"name":"Facultad de Ciencias de la Salud, Laboratorio de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"},{"name":"Departamento de Ciencias B\u00e1sicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga 680002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-7814","authenticated-orcid":false,"given":"Lyda Marcela","family":"Espitia-Perez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Laboratorio de Investigaci\u00f3n Biom\u00e9dica y Biolog\u00eda Molecular, Universidad del Sin\u00fa, Monter\u00eda 230001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2370-1841","authenticated-orcid":false,"given":"Mario","family":"Negrette-Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga 680002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, L., Lu, B., He, M., Wang, Y., Wang, Z., and Du, L. 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