Izmir Biomedicine and Genome Center, Izmir 35340, Turkey.
Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey.
Cells. 2021 Jan 21;10(2):208. doi: 10.3390/cells10020208.
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.
细胞衰老是一种稳定的细胞周期停滞状态，可以响应各种损伤而被触发，其特征是具有独特的形态特征、基因表达谱和衰老相关分泌表型（SASP）。重要的是，细胞衰老作为一种正常生理过程的关键组成部分，具有肿瘤抑制功能。在过去的几十年中，利用促衰老疗法的新型癌症治疗策略引起了相当大的兴趣。然而，最近的研究表明，治疗诱导的衰老（TIS）引发了细胞自主性和非细胞自主性的影响，可能会产生有害的后果，反映了癌细胞衰老的ekyll 和 Hyde 性质。从本质上讲，通常最终导致炎症、癌症干性、衰老逆转、治疗抵抗和疾病复发的不良表现是由衰老细胞和 SASP 的持续积累决定的。因此，通过消除这些细胞或抑制其 SASP 的产生来减轻这些促肿瘤效应，为开发创新的治疗策略提供了巨大的希望。在这篇综述中，我们描述了癌细胞衰老的基本方面和动力学，并总结了关于 TIS 的不良后果的全面研究。此外，我们强调了新兴的衰老治疗方法的原理和动机，即清除衰老细胞和 SASP，以帮助最大限度地提高癌症治疗的整体疗效。
