Morales-Valencia Jorge, David Gregory
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States.
NYU Cancer Institute, New York University School of Medicine, New York, NY, United States.
Front Oncol. 2021 Sep 21;11:747822. doi: 10.3389/fonc.2021.747822. eCollection 2021.
Senescent cells are found to accumulate in aged individuals, as well as in cancer patients that receive chemotherapeutic treatment. Although originally believed to halt cancer progression due to their characteristic growth arrest, senescent cells remain metabolically active and secrete a combination of inflammatory agents, growth factors and proteases, collectively known as the senescence-associated secretory phenotype (SASP). In this review, we discuss the contribution of senescent cells to cancer progression through their ability to alter cancer cells' properties and to generate a microenvironment that promotes tumor growth. Furthermore, recent evidence suggests that senescent cells are able resume proliferation and drive cancer relapse, pointing to the use of senolytics and SASP modulators as a potential approach to prevent tumor resurgence following treatment cessation. Thus, a better understanding of the hallmarks of senescence and the impact of the SASP will allow the development of improved targeted therapeutic strategies to leverage vulnerabilities associated with this cellular state.
衰老细胞在老年人以及接受化疗的癌症患者体内均有积累。尽管最初认为衰老细胞因其特征性的生长停滞而能阻止癌症进展,但它们仍保持代谢活性,并分泌多种炎症因子、生长因子和蛋白酶,这些物质统称为衰老相关分泌表型(SASP)。在本综述中,我们讨论衰老细胞通过改变癌细胞特性以及生成促进肿瘤生长的微环境,从而对癌症进展产生的影响。此外,最近的证据表明衰老细胞能够恢复增殖并导致癌症复发,这表明使用衰老细胞裂解剂和SASP调节剂可能是一种预防治疗停止后肿瘤复发的潜在方法。因此,更好地了解衰老的特征以及SASP的影响,将有助于开发改进的靶向治疗策略,以利用与这种细胞状态相关的脆弱性。