Overcoming the senescence‐associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer. Issue 12 (12th July 2021)

• Record Type: Journal Article
• Authors: Chambers, Cecilia R.; Ritchie, Shona; Pereira, Brooke A.; Timpson, Paul
• Is Part Of: Molecular oncology. Volume 15:Issue 12(2021)
• Page Start: 3242
• Page End: 3255
• Publication Date: 2021-07-12
• Subjects: cancer -- cellular senescence -- senescence‐associated secretory phenotype -- therapy‐induced senescence; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13042
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : In response to therapy or other stimuli, cancer cells can undergo cellular senescence, a stress response leading to cell cycle arrest. An unintended consequence of cellular senescence is a perturbed, pro‐inflammatory cancer cell secretome, the senescence‐associated secretory phenotype (SASP). Here, we explore the role of SASP in promoting tumorigenesis and treatment resistance, with particular focus on mechanisms of therapy‐induced senescence (TIS).