{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:05:19Z","timestamp":1790154319129,"version":"4.0.1"},"reference-count":179,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"MCIU\/AEI\/FEDER, UE","doi-asserted-by":"publisher","award":["PID2024-155394OB-I00"],"award-info":[{"award-number":["PID2024-155394OB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"CIBER de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00275"],"award-info":[{"award-number":["CB16\/12\/00275"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011011","name":"Regional Ministry of Economic Transformation, Industry, Knowledge and Universities of the Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["DGP_PIDI_2024_00907"],"award-info":[{"award-number":["DGP_PIDI_2024_00907"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DGP_PIDI_2024_00907"],"award-info":[{"award-number":["DGP_PIDI_2024_00907"]}],"id":[{"id":"https:\/\/ror.org\/01jem9c82","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NextGenerationEU funds","award":["PMP22\/00092"],"award-info":[{"award-number":["PMP22\/00092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cellular senescence is a heterogeneous and context-dependent stress response that can influence cancer treatment response. Therapy-induced senescence (TIS) may initially suppress tumor growth through durable proliferative arrest, whereas persistence of senescent cells may, in specific contexts, contribute to recurrence or resistance through SASP-mediated signaling, metabolic and epigenetic remodeling, cellular plasticity, immune evasion, and changes in the tumor microenvironment. TIS also develops within tissues that may contain pre-existing senescent populations generated by aging, chronic inflammation, environmental stress, metabolic dysfunction, fibrosis, or oncogenic signaling. In this narrative review, we synthesize mechanistic, translational, and clinical evidence linking senescence to resistance across chemotherapy, radiotherapy, targeted therapy, and immunotherapy. We explicitly distinguish experimental mechanisms, clinical associations, and evidence that has or has not undergone prospective validation. Particular attention is given to SASP signaling, cellular plasticity and cancer stemness, senescence escape, metabolic adaptation, immune surveillance, and biomarker limitations. We further evaluate emerging senolytic and senomorphic strategies and the sequential \u201cone\u2013two punch\u201d paradigm, emphasizing differences between preclinical proof-of-concept and clinical evidence. Overall, current data support a context-dependent role for persistent senescence in treatment resistance, but do not establish TIS as a universal or independent cause of therapeutic failure. Clinical translation remains limited by senescence heterogeneity, lack of validated biomarkers, treatment toxicity, uncertainty regarding timing, and insufficient prospective trials.<\/jats:p>","DOI":"10.3390\/cancers18193084","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:14:39Z","timestamp":1790151279000},"page":"3084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapy-Induced Senescence in Cancer Treatment Resistance: Mechanisms, Evidence, and Translational Opportunities"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-0150","authenticated-orcid":false,"given":"Jose-Ramon","family":"Blanco","sequence":"first","affiliation":[{"name":"Hospital Universitario San Pedro, 26006 Logro\u00f1o, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de La Rioja, 26006 Logro\u00f1o, Spain"},{"name":"Grupo de Investigaci\u00f3n en Cuidados y Salud (GRUPAC), Universidad de La Rioja, 26004 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4357-3979","authenticated-orcid":false,"given":"Amancio","family":"Carnero","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen Del Roc\u00edo (HUVR), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"CIBER de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: When bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. 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