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The tumor suppressor p53 typically coordinates senescence to prevent tumorigenesis, yet p53 mutations or defects in its regulators can derail this program, enabling senescence evasion and therapy resistance. Therapy-induced senescence can paradoxically promote tumor progression through SASP-driven remodeling of the tumor microenvironment controlled by p53-mediated NF-κB signaling. The review evaluates senolytics and immunotherapies and proposes strategic senescence modulation for next-generation anticancer therapy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/therapy-induced-senescence-tis-and-sasp-the-p53-mediated-interplay-in-cancer-progression-and-treatment/461812/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/therapy-induced-senescence-tis-and-sasp-the-p53-mediated-interplay-in-cancer-progression-and-treatment/461812.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-06","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does p53 influence therapy-induced senescence (TIS) and cancer progression?","Question",{"text":112,"@type":113},"p53 coordinates the senescence program that can inhibit tumorigenesis. When p53 is mutated or its regulators are disrupted, the senescence program can be subverted, supporting senescence evasion and therapy resistance. The p53-mediated regulation also dictates SASP-related signaling (including NF-κB), shaping pro-tumor outcomes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does the SASP play in the effects of TIS after treatment?",{"text":117,"@type":113},"Therapy-induced senescence can drive tumor progression by generating a senescence-associated secretory phenotype (SASP). SASP releases inflammatory cytokines, growth factors, and proteases that remodel the local tumor microenvironment, creating a pro-tumorigenic niche that can support recurrence, angiogenesis, and malignant progression.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic strategies does the review discuss for targeting senescence?",{"text":121,"@type":113},"The review evaluates emerging therapies, including senolytics and immunotherapies. It argues that strategic modulation of senescence may offer a promising paradigm for future anticancer treatment by addressing the risks associated with senescent cancer cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},461812,1790834361,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Review  \nTherapy-Induced Senescence (TIS) and SASP: The p53-Mediated Interplay in Cancer Progression and Treatment  \nChang Hoon Lee 1, *, Tuan Minh Nguyen 1, Yongook Lee 1, Seoung Gyu Choi 1, Phuong Ngan Nguyen 1, Jung Ho Park 1 and Mi Kyung Park 2, *  \nAcademic Editor: Jacek Z. Kubiak  \nReceived: 2 December 2025  \nRevised: 23 December 2025  \nAccepted: 26 December 2025  \nPublished: 29 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea  \n2 Department of Biomedical Science, Hwasung Medi-Science University, Hwaseong-si 18274, Republic of Korea  \n* [Correspondence: uatheone@dongguk.edu](Correspondence: uatheone@dongguk.edu) (C.H.L.); [mkpark@hsmu.ac.kr](mkpark@hsmu.ac.kr) (M.K.P.)  \nAbstract  \nCellular senescence, initially regarded as a potent tumor-suppressive mechanism, is now recognized as a double-edged sword that modulates the hallmarks of cancer. The tumor suppressor p53 typically orchestrates this process to inhibit tumorigenesis; however, mutations in p53 or its regulators can subvert this program, leading to senescence evasion and therapy resistance. In particular, therapy-induced senescence can paradoxically drive tumor progression via the senescence-associated secretory phenotype, which creates a pro-tumorigenic microenvironment dictated by p53-mediated regulation of NF-κB signaling. Here, we explore the p53-mediated senescence–cancer interplay and evaluate emerging therapies, including senolytics and immunotherapies. We propose that strategic modulation of senescence offers a promising paradigm for future anticancer therapy.  \nKeywords: cellular senescence; p53; therapy-induced senescence (TIS); senescenceassociated secretory phenotype (SASP); senolytics; senomorphics; cancer immunotherapy  \n1. Introduction  \nFor decades, anticancer therapy has centered on inhibiting uncontrolled proliferation and inducing cellular demise of malignant cells. Conventional strategies—chiefly chemotherapy and radiotherapy—represent the cornerstones of this approach and have substantially extended the survival of countless patients.  \nDespite these advances, therapeutic resistance and subsequent tumor recurrence—driven by the persistence of residual cancer cells that survive treatment—remain the most formidable challenges in modern oncology. Overcoming this clinical impasse is paramount [1,2] .  \nAt the heart of this limitation lies cellular senescence. Defined as a state of stable and permanent cell cycle arrest, senescence is triggered in response to various forms of cellular stress or damage. It was initially recognized as a critical intrinsic defense mechanism that suppresses tumorigenesis, primarily induced by key tumor-suppressive pathways such as those governed by p53 (the guardian of the genome) and the p16/Rb (retinoblastoma protein) pathway [3] .  \nHowever, emerging research has revealed that this protective barrier can paradoxically become a promoter of malignancy under specific conditions. A primary concern is therapy-induced senescence (TIS), which arises when cancer cells evade apoptosis following treatment and instead enter a stable senescent state.  \nThese persistent senescent cells, often referred to as a distinct pathological identity, acquire a detrimental function by releasing a complex pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP) . The SASP comprises a diverse array of inflammatory cytokines, growth factors, and proteases that actively remodel the local tumor microenvironment (TME) . This remodeling creates a pro-tumorigenic niche that promotes tumor recurrence, angiogenesis, and malignant progression [4] . Therefore, elucidating the mechanisms of TIS and developi","cbCaimFnGYSyjmXZ","https://ap.wps.com/l/cbCaimFnGYSyjmXZ","pdf",3232198,28,"English","# 1. Introduction\n## Cellular senescence and therapy resistance\n## p53-mediated control of TIS and SASP\n## Clinical controversy and review focus\n# 2. Understanding Cellular Senescence\n## Triggers and master regulatory pathways","[{\"question\":\"How does p53 influence therapy-induced senescence (TIS) and cancer progression?\",\"answer\":\"p53 coordinates the senescence program that can inhibit tumorigenesis. When p53 is mutated or its regulators are disrupted, the senescence program can be subverted, supporting senescence evasion and therapy resistance. The p53-mediated regulation also dictates SASP-related signaling (including NF-κB), shaping pro-tumor outcomes.\"},{\"question\":\"What role does the SASP play in the effects of TIS after treatment?\",\"answer\":\"Therapy-induced senescence can drive tumor progression by generating a senescence-associated secretory phenotype (SASP). SASP releases inflammatory cytokines, growth factors, and proteases that remodel the local tumor microenvironment, creating a pro-tumorigenic niche that can support recurrence, angiogenesis, and malignant progression.\"},{\"question\":\"What therapeutic strategies does the review discuss for targeting senescence?\",\"answer\":\"The review evaluates emerging therapies, including senolytics and immunotherapies. It argues that strategic modulation of senescence may offer a promising paradigm for future anticancer treatment by addressing the risks associated with senescent cancer cells.\"}]","Therapy-Induced Senescence (TIS) and SASP - The p53-Mediated Interplay in Cancer Progression and Treatment | PDF",1790762483,71]