肉瘤中涉及转录因子和染色质调节因子的显性融合癌蛋白的生物学和治疗

IF 4.7 2区 医学 Q1 ONCOLOGY Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI:10.1146/ANNUREV-CANCERBIO-030518-055710
J. Perry, B. Seong, K. Stegmaier
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引用次数: 18

摘要

三分之一的软组织肉瘤已被证明携带复发性、特征性的染色体易位,其中许多产生融合蛋白,作为显性转录因子或染色质调节因子。随着大规模平行测序的常规使用以及表观遗传学和蛋白质复合物研究技术的进步,过去十年在鉴定新的融合体以及我们对它们导致恶性状态的机制的理解方面取得了显著进展。此外,随着化学中的新方法,如靶向蛋白质降解策略,我们现在可以更好地解决这些以前难以解决的目标。在这篇综述中,我们描述了三种最常见的融合驱动型肉瘤(尤文氏肉瘤、肺泡横纹肌肉瘤和滑膜肉瘤),这些疾病出现的机制主题,以及它们的靶向治疗的新方法。
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Biology and Therapy of Dominant Fusion Oncoproteins Involving Transcription Factor and Chromatin Regulators in Sarcomas
A third of soft tissue sarcomas have been shown to carry recurrent, characteristic chromosomal translocations, many of which generate fusion proteins that act as dominant transcription factors or as chromatin regulators. With routine use of massively parallel sequencing and advances in technology for the study of epigenetics and protein complexes, the last decade has seen a marked advancement in the identification of novel fusions and in our understanding of the mechanisms by which they contribute to the malignant state. Moreover, with new approaches in chemistry, such as the strategy of targeted protein degradation, we are now better poised to address these previously intractable targets. In this review, we describe three of the most common fusion-driven sarcomas (Ewing sarcoma, alveolar rhabdomyosarcoma, and synovial sarcoma), mechanistic themes emerging across these diseases, and novel approaches to their targeting.
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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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