{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:29:35Z","timestamp":1777498175283,"version":"3.51.4"},"reference-count":381,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006742","name":"CESPU\u2014Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio Crl","doi-asserted-by":"publisher","award":["FlavCanAct-GI2-CESPU-2025"],"award-info":[{"award-number":["FlavCanAct-GI2-CESPU-2025"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006742","name":"CESPU\u2014Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio Crl","doi-asserted-by":"publisher","award":["TargetMito-GI2-CESPU-2025"],"award-info":[{"award-number":["TargetMito-GI2-CESPU-2025"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006742","name":"CESPU","doi-asserted-by":"publisher","award":["BD\/CBAS\/CESPU\/01\/2020"],"award-info":[{"award-number":["BD\/CBAS\/CESPU\/01\/2020"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006742","name":"CESPU","doi-asserted-by":"publisher","award":["BD\/CBAS\/CESPU\/01\/2021"],"award-info":[{"award-number":["BD\/CBAS\/CESPU\/01\/2021"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2022.09451.BD"],"award-info":[{"award-number":["2022.09451.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellular responses to chemotherapy, often conferring drug resistance. Additional non-apoptotic functions, including roles in metabolism, mitochondrial dynamics, and cellular homeostasis, further expand their biological relevance. Clinical trials exploring strategies to inhibit BCL-2 and BCL-xL, including selective BH3 mimetics and combination regimens, are discussed with emphasis on their potential and limitations in oncology. Overall, this review highlights the multifaceted contributions of BCL-2 and BCL-xL to cancer biology and underscores the importance of continued efforts to refine targeted therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms27021123","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-4286","authenticated-orcid":false,"given":"Jo\u00e3o P. 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A.","family":"Silva","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences\u2014CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-5779","authenticated-orcid":false,"given":"Hassan","family":"Bousbaa","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences\u2014CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.12688\/f1000research.21571.1","article-title":"The Essentials of Developmental Apoptosis","volume":"9","author":"Voss","year":"2020","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.mad.2016.04.007","article-title":"A Brewing Understanding of the Regulation of Bax Function by Bcl-XL and Bcl-2","volume":"161","author":"Renault","year":"2017","journal-title":"Mech. 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