基因组稳定性受染色质结构动力学的控制，除了 ATP 依赖性染色质重塑剂的活性外，染色质结构动力学还会在核小体内和核小体间接触、组蛋白翻译后修饰 (PTM) 和变异的影响下改变 DNA 的可及性。这些是染色质动态调节和与核过程相关的主要方式，当核过程失调时，通常与大多数恶性肿瘤有关。最近，组蛋白修饰和染色质重塑之间的功能串扰已成为细胞命运选择过程中转录调控的关键调控方法。因此，通过关注恶性肿瘤中失调的表观遗传靶标来改善患者的治疗结果应该有助于防止癌细胞对抗癌治疗产生耐药性。因此，SET 结构域分叉组蛋白赖氨酸甲基转移酶 1 (SETDB1) 最近作为癌症靶点受到了广泛关注。 SETDB1 是一种组蛋白赖氨酸甲基转移酶，在标记常染色质和异染色质区域中发挥重要作用。因此，它促进肿瘤抑制基因的沉默并有助于致癌作用。一些研究表明，SETDB1 在多种人类癌症类型中过度表达，从而促进肿瘤生长和转移。因此，SETDB1 似乎是新癌症治疗的一个有吸引力的表观遗传靶点。在这篇综述中，我们讨论了其过度表达对肿瘤进展的影响以及专门针对这种酶的抑制剂药物的开发。该期刊版权所有©英国皇家化学学会。

Genome stability is governed by chromatin structural dynamics, which modify DNA accessibility under the influence of intra- and inter-nucleosomal contacts, histone post-translational modifications (PTMs) and variations, besides the activity of ATP-dependent chromatin remodelers. These are the main ways by which chromatin dynamics are regulated and connected to nuclear processes, which when dysregulated can frequently be associated with most malignancies. Recently, functional crosstalk between histone modifications and chromatin remodeling has emerged as a critical regulatory method of transcriptional regulation during cell destiny choice. Therefore, improving therapeutic outcomes for patients by focusing on epigenetic targets dysregulated in malignancies should help prevent cancer cells from developing resistance to anticancer treatments. For this reason, SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) has gained a lot of attention recently as a cancer target. SETDB1 is a histone lysine methyltransferase that plays an important role in marking euchromatic and heterochromatic regions. Hence, it promotes the silencing of tumor suppressor genes and contributes to carcinogenesis. Some studies revealed that SETDB1 was overexpressed in various human cancer types, which enhanced tumor growth and metastasis. Thus, SETDB1 appears to be an attractive epigenetic target for new cancer treatments. In this review, we have discussed the effects of its overexpression on the progression of tumors and the development of inhibitor drugs that specifically target this enzyme.This journal is © The Royal Society of Chemistry.