{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:36:20Z","timestamp":1789875380113,"version":"4.0.1"},"reference-count":159,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["2023\/51\/B\/NZ5\/00498"],"award-info":[{"award-number":["2023\/51\/B\/NZ5\/00498"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cellular senescence is defined as a state of permanent cell cycle arrest, providing a natural barrier against cancer. However, senescent cells are very metabolically active and secrete a complex mixture of bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP), which play a dual role in cancer biology. While the SASP can suppress tumors by facilitating immunosurveillance, it can also promote tumor progression by fostering a pro-inflammatory milieu, stimulating angiogenesis, enhancing invasiveness, and enabling immune evasion. In Head and Neck Cancers (HNCs), a highly heterogeneous group of malignancies, SASP has emerged as a critical player in disease progression and treatment resistance. Persistent DNA damage response (DDR) signaling drives SASP and thereby contributes to the progression of head and neck cancer by modulating the tumour microenvironment. It influences the tumor microenvironment (TME) by facilitating epithelial-to-mesenchymal transition (EMT), promoting cancer stem cell-like properties, and impairing the efficacy of radiotherapy, chemotherapy, and immune checkpoint inhibitors. These effects underscore the need for targeted interventions to regulate SASP activity. This review presents a comprehensive overview of the molecular mechanisms underlying SASP generation and its effects on HNCs. We discuss the dual roles of SASP in tumor suppression and progression, its contribution to therapy resistance, and emerging therapeutic strategies, including novel senolytic and senomorphic drugs. Finally, we highlight key challenges and future directions for translating SASP-targeted therapies into clinical practice, emphasizing the need for biomarker discovery, and a deeper understanding of SASP heterogeneity. By targeting the SASP, there is potential to enhance therapeutic outcomes and improve the management of HNCs.<\/jats:p>","DOI":"10.3390\/cancers17244024","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:42:52Z","timestamp":1765978972000},"page":"4024","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Impact of Senescence-Associated Secretory Phenotype (SASP) on Head and Neck Cancers: From Biology to Therapy"],"prefix":"10.3390","volume":"17","author":[{"given":"Md Tanjim","family":"Alam","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4930-0552","authenticated-orcid":false,"given":"Mishfak A. M.","family":"Mansoor","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Ashiqueali","sequence":"additional","affiliation":[{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Golusinski","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Maxillofacial Surgery, University of Zielona Gora, 65-417 Zielona Gora, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-2670","authenticated-orcid":false,"given":"Ewelina","family":"Golusinska-Kardach","sequence":"additional","affiliation":[{"name":"Department of Dental Surgery, Periodontology and Oral Mucosa Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-5685","authenticated-orcid":false,"given":"Joanna K.","family":"Strzelczyk","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-0176","authenticated-orcid":false,"given":"Blazej","family":"Rubis","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 61-707 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Golusinski","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal M.","family":"Masternak","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA"},{"name":"Department of Head and Neck Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. 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