Division of Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
Division of Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, 3052, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, 3052, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3168, Australia.
Mech Ageing Dev. 2020 Apr;187:111229. doi: 10.1016/j.mad.2020.111229. Epub 2020 Mar 18.
Oncogene-induced senescence (OIS) is a powerful intrinsic tumor-suppressive mechanism, arresting cell cycle progression upon oncogene-activating genomic alterations. The discovery and characterization of the senescence-associated secretome unveiled a rich additional complexity to the senescence phenotype, including extrinsic impacts on the microenvironment and engagement of the immune response. Emerging evidence suggests that senescence phenotypes vary depending on the oncogenic stimulus. Therefore, understanding the mechanisms underlying OIS and how they are subverted in cancer will provide invaluable opportunities to identify alternative strategies for treating oncogene-driven cancers. In this review, we primarily discuss the key mechanisms governing OIS driven by the RAS/MAPK and PI3K/AKT pathways and how understanding the biology of senescent cells has uncovered new therapeutic possibilities to target cancer.
癌基因诱导的衰老（OIS）是一种强大的内在肿瘤抑制机制，可在癌基因激活的基因组改变时阻止细胞周期进程。衰老相关分泌表型的发现和特征揭示了衰老表型的丰富的额外复杂性，包括对微环境的外在影响和对免疫反应的参与。新出现的证据表明，衰老表型取决于致癌刺激。因此，了解 OIS 的潜在机制以及它们在癌症中如何被颠覆，将为确定治疗致癌基因驱动的癌症的替代策略提供宝贵的机会。在这篇综述中，我们主要讨论了由 RAS/MAPK 和 PI3K/AKT 途径驱动的 OIS 的关键机制，以及了解衰老细胞的生物学如何揭示了靶向癌症的新的治疗可能性。
