Shenzhen University School of Medicine, Shenzhen 518060, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
Curr Med Chem. 2019;26(8):1328-1350. doi: 10.2174/0929867324666170921101947.
Epigenetics is defined as somatically inheritable changes that are not accompanied by alterations in DNA sequence. Epigenetics encompasses DNA methylation, covalent histone modifications, non-coding RNA as well as nucleosome remodeling. Notably, abnormal epigenetic changes play a critical role in cancer development including malignant transformation, metastasis, prognosis, drug resistance and tumor recurrence, which can provide effective targets for cancer prognosis, diagnosis and therapy. Understanding these changes provide effective means for cancer diagnosis and druggable targets for better clinical applications. Histone modifications and related enzymes have been found to correlate well with cancer incidence and prognosis in recent years. Dysregulated expression or mutation of histone modification enzymes and histone modification status abnormalities have been considered to play essential roles in tumorigenesis and clinical outcomes of cancer treatment. Some of the histone modification inhibitors have been extensively employed in clinical practice and many others are still under laboratory research or pre-clinical assessment. Here we summarize the important roles of epigenetics, especially histone modifications in cancer diagnostics and therapeutics, and also discuss the developmental implications of activatable epigenetic targets in cancer theranostics.
表观遗传学被定义为不伴随 DNA 序列改变的体细胞核遗传变化。表观遗传学包括 DNA 甲基化、组蛋白共价修饰、非编码 RNA 以及核小体重塑。值得注意的是，异常的表观遗传变化在癌症的发展中起着关键作用，包括恶性转化、转移、预后、耐药和肿瘤复发，这为癌症的预后、诊断和治疗提供了有效的靶点。了解这些变化为癌症的诊断提供了有效的手段，并为更好的临床应用提供了可用药的靶点。近年来，组蛋白修饰及其相关酶已被发现与癌症的发生和预后密切相关。组蛋白修饰酶的表达或突变失调以及组蛋白修饰状态异常被认为在肿瘤发生和癌症治疗的临床结果中起重要作用。一些组蛋白修饰抑制剂已广泛应用于临床实践，还有许多其他抑制剂仍处于实验室研究或临床前评估阶段。本文总结了表观遗传学，特别是组蛋白修饰在癌症诊断和治疗中的重要作用，并讨论了可激活的表观遗传靶点在癌症治疗中的发展意义。
