Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Department of Urology, New York University School of Medicine, New York, NY, USA.
Expert Opin Ther Targets. 2019 Dec;23(12):1041-1051. doi: 10.1080/14728222.2019.1565658. Epub 2019 Jan 15.
: Cellular senescence is a stable form of cell cycle exit. Though they no longer divide, senescent cells remain metabolically active and secrete a plethora of proteins collectively termed the senescence-associated secretory phenotype (SASP). Although senescence-associated cell cycle exit likely evolved as an anti-tumor mechanism, the SASP contains both anti- and pro-tumorigenic potential.: In this review, we briefly discuss the discovery of senescent cells and its relationship to cancer and aging. We also describe the initiation and regulation of the SASP upon senescence stimulus onset. We focus on both the pro- and anti-tumorigenic properties of the SASP. Finally, we speculate on the potential benefits of therapy-induced senescence combined with selective SASP inhibition for the treatment of cancer.: Further identification and characterization of the SASP factors that are pro-tumorigenic and those that are anti-tumorigenic in specific contexts will be crucial in order to develop personalized therapeutics for the successful treatment of cancer.
细胞衰老(cellular senescence)是细胞周期退出的一种稳定形式。尽管衰老细胞不再分裂,但它们仍然保持代谢活性并分泌大量蛋白质,这些蛋白质统称为衰老相关分泌表型(SASP)。尽管衰老相关的细胞周期退出可能是作为一种抗肿瘤机制而进化的,但 SASP 既包含抗肿瘤潜能,也包含促肿瘤潜能。
在这篇综述中,我们简要讨论了衰老细胞的发现及其与癌症和衰老的关系。我们还描述了衰老刺激开始时 SASP 的启动和调节。我们重点讨论了 SASP 的促肿瘤和抗肿瘤特性。最后,我们推测诱导性衰老与选择性 SASP 抑制相结合治疗癌症的潜在益处。
为了成功治疗癌症,开发针对特定情况的促肿瘤和抗肿瘤 SASP 因子的个体化治疗方法,进一步鉴定和表征 SASP 因子将至关重要。