Selim Omar, Song Clara, Kumar Amy, Phelan Rebecca, Singh Arun, Federman Noah
Clinical and Translational Science Institute, University of California, Los Angeles, CA, United States.
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, United States.
Front Oncol. 2023 Aug 18;13:1244035. doi: 10.3389/fonc.2023.1244035. eCollection 2023.
This review aims to summarize the putative role of histone deacetylases (HDACs) in rhabdomyosarcoma (RMS) and the effects of HDAC inhibitors (HDACi) on RMS by elucidating and highlighting known oncogenic pathways, mechanisms of resistance, and the synergistic potential of histone deacetylase inhibitors. We searched two databases (PubMed and Google Scholar) for the keywords "Rhabdomyosarcoma, histone deacetylase, histone deacetylase inhibitors." We excluded three publications that did not permit access to the full text to review and those that focus exclusively on pleiomorphic RMS in adults. Forty-seven papers met the inclusion criteria. This review highlights that HDACi induce cytotoxicity, cell-cycle arrest, and oxidative stress in RMS cells. Ultimately, HDACi have been shown to increase apoptosis and the cessation of embryonal and alveolar RMS proliferation and , both synergistically and on its own. HDACi contain potent therapeutic potential against RMS. This review discusses the significant findings and the biological mechanisms behind the anti-cancer effects of HDACi. Additionally, this review highlights important clinical trials assessing the efficacy of HDACi in sarcomas.
本综述旨在通过阐明和强调已知的致癌途径、耐药机制以及组蛋白去乙酰化酶抑制剂（HDACi）的协同潜力，总结组蛋白去乙酰化酶（HDACs）在横纹肌肉瘤（RMS）中的假定作用以及HDACi对RMS的影响。我们在两个数据库（PubMed和谷歌学术）中搜索了关键词“横纹肌肉瘤、组蛋白去乙酰化酶、组蛋白去乙酰化酶抑制剂”。我们排除了三篇无法获取全文以供审查的出版物以及那些专门关注成人多形性RMS的出版物。47篇论文符合纳入标准。本综述强调HDACi可诱导RMS细胞产生细胞毒性、细胞周期停滞和氧化应激。最终，HDACi已被证明可增加细胞凋亡，并协同或单独地使胚胎性和肺泡性RMS的增殖停止。HDACi对RMS具有强大的治疗潜力。本综述讨论了HDACi抗癌作用背后的重要发现和生物学机制。此外，本综述强调了评估HDACi在肉瘤中疗效的重要临床试验。
