内源性逆转录因子在癌症发展和治疗中的再激活

IF 4.7 2区 医学 Q1 ONCOLOGY
Charles A. Ishak, D. D. Carvalho
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引用次数: 34

摘要

驯化的逆转录因子作为调控元件在宿主基因网络中发挥着广泛的作用。在种系整合后,通过表观遗传沉默、突变降解和被描述为病毒模仿反应的先天免疫防御,逆转录因子的动员受到限制。最近的发现揭示了肿瘤发生的早期事件如何重新激活逆转录因子以促进肿瘤共移除、复制应激、逆转录转位、有丝分裂错误和无菌炎症,这些都破坏了基因组的完整性。癌细胞中逆转录因子改变的表观遗传稳态的特征也揭示了新的表观遗传靶点,其失活可以增强对癌症治疗的反应。本文回顾了最近的发现,认为重新激活的逆转录因子既是肿瘤发生的驱动因素,也是治疗反应的驱动因素,新兴的表观遗传疗法可以增强免疫检查点阻断、癌症疫苗和其他标准疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Reactivation of Endogenous Retroelements in Cancer Development and Therapy
Domesticated retroelements contribute extensively as regulatory elements within host gene networks. Upon germline integration, retroelement mobilization is restricted through epigenetic silencing, mutational degradation, and innate immune defenses described as the viral mimicry response. Recent discoveries reveal how early events in tumorigenesis reactivate retroelements to facilitate onco-exaptation, replication stress, retrotransposition, mitotic errors, and sterile inflammation, which collectively disrupt genome integrity. The characterization of altered epigenetic homeostasis at retroelements in cancer cells also reveals new epigenetic targets whose inactivation can bolster responses to cancer therapies. Recent discoveries reviewed here frame reactivated retroelements as both drivers of tumorigenesis and therapy responses, where their reactivation by emerging epigenetic therapies can potentiate immune checkpoint blockade, cancer vaccines, and other standard therapies.
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来源期刊
CiteScore
14.50
自引率
1.30%
发文量
13
期刊介绍: The Annual Review of Cancer Biology offers comprehensive reviews on various topics within cancer research, covering pivotal and emerging areas in the field. As our understanding of cancer's fundamental mechanisms deepens and more findings transition into targeted clinical treatments, the journal is structured around three main themes: Cancer Cell Biology, Tumorigenesis and Cancer Progression, and Translational Cancer Science. The current volume of this journal has transitioned from gated to open access through Annual Reviews' Subscribe to Open program, ensuring all articles are published under a CC BY license.
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