The Jekyll and Hyde of Cellular Senescence in Cancer
1
Izmir Biomedicine and Genome Center, Izmir 35340, Turkey
2
Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2021, 10(2), 208; https://doi.org/10.3390/cells10020208
Received: 23 December 2020 / Revised: 15 January 2021 / Accepted: 17 January 2021 / Published: 21 January 2021
(This article belongs to the Special Issue Mechanisms of Aging and Therapeutic Approaches to Target Age-Associated Chronic Diseases)
Cellular senescence is a state of stable cell cycle arrest that can be triggered in response to various insults and is characterized by distinct morphological hallmarks, gene expression profiles, and the senescence-associated secretory phenotype (SASP). Importantly, cellular senescence is a key component of normal physiology with tumor suppressive functions. In the last few decades, novel cancer treatment strategies exploiting pro-senescence therapies have attracted considerable interest. Recent insight, however, suggests that therapy-induced senescence (TIS) elicits cell-autonomous and non-cell-autonomous implications that potentially entail detrimental consequences, reflecting the Jekyll and Hyde nature of cancer cell senescence. In essence, the undesirable manifestations that generally culminate in inflammation, cancer stemness, senescence reversal, therapy resistance, and disease recurrence are dictated by the persistent accumulation of senescent cells and the SASP. Thus, mitigating these pro-tumorigenic effects by eliminating these cells or inhibiting their SASP production holds great promise for developing innovative therapeutic strategies. In this review, we describe the fundamental aspects and dynamics of cancer cell senescence and summarize the comprehensive research on the adverse outcomes of TIS. Furthermore, we underline the rationale and motivation of emerging senotherapeutic modalities surrounding the removal of senescent cells and the SASP to help maximize the overall efficacy of cancer therapies.
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Keywords:
cancer; cellular senescence; SASP; therapy-induced senescence; senostatic; senolytic
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MDPI and ACS Style
Demirci, D.; Dayanc, B.; Mazi, F.A.; Senturk, S. The Jekyll and Hyde of Cellular Senescence in Cancer. Cells 2021, 10, 208. https://doi.org/10.3390/cells10020208
AMA Style
Demirci D, Dayanc B, Mazi FA, Senturk S. The Jekyll and Hyde of Cellular Senescence in Cancer. Cells. 2021; 10(2):208. https://doi.org/10.3390/cells10020208
Chicago/Turabian StyleDemirci, Dilara; Dayanc, Bengisu; Mazi, Fatma A.; Senturk, Serif. 2021. "The Jekyll and Hyde of Cellular Senescence in Cancer" Cells 10, no. 2: 208. https://doi.org/10.3390/cells10020208
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