Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer

Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells...

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Autores principales:	Cecilia R. Chambers, Shona Ritchie, Brooke A. Pereira, Paul Timpson
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cancer cellular senescence senescence‐associated secretory phenotype therapy‐induced senescence Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3c42425e58964fee97e18d1c95d1e7dd
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spelling	oai:doaj.org-article:3c42425e58964fee97e18d1c95d1e7dd2021-12-02T10:31:06ZOvercoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer1878-02611574-789110.1002/1878-0261.13042https://doaj.org/article/3c42425e58964fee97e18d1c95d1e7dd2021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13042https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells of the tumour microenvironment can remain metabolically active, resulting in paradoxical secretion of pro‐inflammatory factors, collectively termed the senescence‐associated secretory phenotype (SASP). The SASP plays a critical role in tumorigenesis, affecting numerous processes including invasion, metastasis, epithelial‐to‐mesenchymal transition (EMT) induction, therapy resistance and immunosuppression. With increasing evidence, it is becoming clear that cell type, tissue of origin and the primary cellular stressor are key determinants in how the SASP will influence tumour development and progression, including whether it will be pro‐ or antitumorigenic. In this review, we will focus on recent evidence regarding therapy‐induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy. We will also discuss novel pharmacological manipulation of senescent cancer cells and the SASP, which offers an exciting and contemporary approach to cancer therapeutics. With future research, these adjuvant options may help to mitigate many of the negative side effects and protumorigenic roles that are currently associated with TIS in cancer.Cecilia R. ChambersShona RitchieBrooke A. PereiraPaul TimpsonWileyarticlecancercellular senescencesenescence‐associated secretory phenotypetherapy‐induced senescenceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3242-3255 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer cellular senescence senescence‐associated secretory phenotype therapy‐induced senescence Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cancer cellular senescence senescence‐associated secretory phenotype therapy‐induced senescence Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cecilia R. Chambers Shona Ritchie Brooke A. Pereira Paul Timpson Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer
description	Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells of the tumour microenvironment can remain metabolically active, resulting in paradoxical secretion of pro‐inflammatory factors, collectively termed the senescence‐associated secretory phenotype (SASP). The SASP plays a critical role in tumorigenesis, affecting numerous processes including invasion, metastasis, epithelial‐to‐mesenchymal transition (EMT) induction, therapy resistance and immunosuppression. With increasing evidence, it is becoming clear that cell type, tissue of origin and the primary cellular stressor are key determinants in how the SASP will influence tumour development and progression, including whether it will be pro‐ or antitumorigenic. In this review, we will focus on recent evidence regarding therapy‐induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy. We will also discuss novel pharmacological manipulation of senescent cancer cells and the SASP, which offers an exciting and contemporary approach to cancer therapeutics. With future research, these adjuvant options may help to mitigate many of the negative side effects and protumorigenic roles that are currently associated with TIS in cancer.
format	article
author	Cecilia R. Chambers Shona Ritchie Brooke A. Pereira Paul Timpson
author_facet	Cecilia R. Chambers Shona Ritchie Brooke A. Pereira Paul Timpson
author_sort	Cecilia R. Chambers
title	Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer
title_short	Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer
title_full	Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer
title_fullStr	Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer
title_full_unstemmed	Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer
title_sort	overcoming the senescence‐associated secretory phenotype (sasp): a complex mechanism of resistance in the treatment of cancer
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/3c42425e58964fee97e18d1c95d1e7dd
work_keys_str_mv	AT ceciliarchambers overcomingthesenescenceassociatedsecretoryphenotypesaspacomplexmechanismofresistanceinthetreatmentofcancer AT shonaritchie overcomingthesenescenceassociatedsecretoryphenotypesaspacomplexmechanismofresistanceinthetreatmentofcancer AT brookeapereira overcomingthesenescenceassociatedsecretoryphenotypesaspacomplexmechanismofresistanceinthetreatmentofcancer AT paultimpson overcomingthesenescenceassociatedsecretoryphenotypesaspacomplexmechanismofresistanceinthetreatmentofcancer
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Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer

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