European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, 9713AV Groningen, The Netherlands.
European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, 9713AV Groningen, The Netherlands.
Trends Cancer. 2020 Oct;6(10):838-857. doi: 10.1016/j.trecan.2020.05.004. Epub 2020 May 29.
Several cancer interventions induce DNA damage and promote senescence in cancer and nonmalignant cells. Senescent cells secrete a collection of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP). SASP factors are able to potentiate various aspects of tumorigenesis, including proliferation, metastasis, and immunosuppression. Moreover, the accumulation and persistence of therapy-induced senescent cells can promote tissue dysfunction and the early onset of various age-related symptoms in treated cancer patients. Here, we review in detail the mechanisms by which cellular senescence contributes to cancer development and the side effects of cancer therapies. We also review how pharmacological interventions to eliminate senescent cells or inhibit SASP production can mitigate these negative effects and propose therapeutic strategies based on the age of the patient.
几种癌症干预措施会在癌症和非恶性细胞中诱导 DNA 损伤并促进衰老。衰老细胞会分泌一组被称为衰老相关分泌表型 (SASP) 的促炎因子。SASP 因子能够增强肿瘤发生的各个方面,包括增殖、转移和免疫抑制。此外,治疗诱导的衰老细胞的积累和持续存在会促进组织功能障碍,并导致治疗后的癌症患者出现各种与年龄相关的早期症状。在这里,我们详细回顾了细胞衰老促进癌症发展和癌症治疗副作用的机制。我们还回顾了如何通过药理学干预消除衰老细胞或抑制 SASP 产生来减轻这些负面影响,并根据患者的年龄提出治疗策略。