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用组蛋白去乙酰化酶抑制剂攻克三阴性乳腺癌:6 是关键同工型!

Tackling triple negative breast cancer with HDAC inhibitors: 6 is the isoform!

机构信息

Department of Pharmacy (DoE 2023-2027), University of Naples Federico II, via D. Montesano 49, 80131, Naples, Italy.

Department of Pharmacy (DoE 2023-2027), University of Naples Federico II, via D. Montesano 49, 80131, Naples, Italy.

出版信息

Eur J Med Chem. 2024 Dec 5;279:116884. doi: 10.1016/j.ejmech.2024.116884. Epub 2024 Sep 16.

Abstract

Triple negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterized by the lack in the expression of estrogen and progesterone receptors, and human epidermal growth factor receptors 2. TNBC stands out among other breast cancers subtypes for its high aggressiveness and invasiveness, and for the limited therapeutic options available, which justify the poor survival rates registered for this breast cancer subtype. Compelling new evidence pointed out the role of epigenetic modifications in cancer, prompting tumor cell uncontrolled proliferation, epithelial-to-mesenchymal transition, and metastatic events. In this review we showcase the latest evidence supporting the involvement of histone deacetylase 6 (HDAC6) in cancer pathways strictly related to TNBC subtype, also tracking the latest advancements in the identification of novel HDAC6 inhibitors which showed efficacy in TNBC models, offering insights into the potential of targeting this key epigenetic player as an innovative therapeutic option for the treatment of TNBC.

摘要

三阴性乳腺癌(TNBC)是一种高度侵袭性的乳腺癌亚型,其特征是缺乏雌激素和孕激素受体以及人表皮生长因子受体 2 的表达。与其他乳腺癌亚型相比,TNBC 的侵袭性和侵袭性更强,治疗选择有限,这也解释了该乳腺癌亚型存活率低的原因。令人信服的新证据指出了表观遗传修饰在癌症中的作用,促使肿瘤细胞不受控制地增殖、上皮-间充质转化和转移事件。在这篇综述中,我们展示了最新的证据,支持组蛋白去乙酰化酶 6(HDAC6)在与 TNBC 亚型密切相关的癌症途径中的作用,同时还跟踪了鉴定新型 HDAC6 抑制剂的最新进展,这些抑制剂在 TNBC 模型中显示出了疗效,为靶向这种关键的表观遗传因子作为治疗 TNBC 的创新治疗选择提供了思路。

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