Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer is defined by the absence of hormone receptor and growth factor receptor ERBB2/HER2 expression. It is characterized by a more aggressive course of disease and a shortage of effective therapeutic approaches. Hallmarks of cancer cells are not only genetic alterations, but also epigenetic aberrations. The most studied and best understood alterations are methylation of the DNA base cytosine and the covalent modification of histone proteins. The reversibility of these covalent modifications make them attractive targets for therapeutic intervention, as documented in numerous ongoing clinical trials. Epidrugs, targeting DNA methylation and histone modifications, might offer attractive new options in treating triple-negative breast cancer. Currently, the most promising options are combination therapies in which the epidrug increases the efficiency of immuncheckpoint inhibitors. This review focusses exclusively on DNA methylation and histone modifications. In reviewing the knowledge about epigenetic therapies in breast cancer, and especially triple-negative breast cancer, the focus is on explaining concepts and raising awareness of what is not yet known and what has to be clarified in the future.
乳腺癌作为全球女性中最常见的恶性肿瘤，在分子层面和临床上均表现出高度异质性。三阴性乳腺癌以缺乏激素受体及生长因子受体ERBB2/HER2表达为特征，其病程更具侵袭性且缺乏有效治疗手段。癌细胞的标志性特征不仅包括基因变异，还涉及表观遗传异常。目前研究最深入的表观遗传改变包括DNA胞嘧啶碱基甲基化及组蛋白共价修饰。这些共价修饰的可逆性使其成为极具潜力的治疗干预靶点，这一点已在众多进行中的临床试验中得到验证。针对DNA甲基化和组蛋白修饰的表观遗传药物，可能为三阴性乳腺癌治疗提供具有吸引力的新选择。当前最具前景的治疗方案是联合疗法，即通过表观遗传药物增强免疫检查点抑制剂的疗效。本综述聚焦于DNA甲基化与组蛋白修饰两大领域，系统梳理乳腺癌（特别是三阴性乳腺癌）表观遗传治疗的研究进展，重点阐释核心概念，并揭示当前认知空白及未来需深入探索的方向。
Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges
肿瘤(癌症)患者之家