Akar Remzi Okan, Selvi Selin, Ulukaya Engin, Aztopal Nazlıhan
Department of Cancer Biology and Pharmacology, Institute of Health Sciences, İstinye University, İstanbul, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, İstinye University, İstanbul, Turkey.
Turk J Biol. 2019 Jun 13;43(3):155-170. doi: 10.3906/biy-1903-39. eCollection 2019.
Epigenetic reprogramming plays a crucial role in the tumorigenicity and maintenance of tumor-specific gene expression that especially occurs through DNA methylation and/or histone modifications. It has well-defined mechanisms. It is known that alterations in the DNA methylation pattern and/or the loss of specific histone acetylation/methylation markers are related to several hallmarks of cancer, such as drug resistance, stemness, epithelial-mesenchymal transition, and metastasis. It has also recently been highlighted that epigenetic alterations are critical for the regulation of the stemlike properties of cancer cells (tumor-initiating cells; cancer stem cells). Cancer stem cells are thought to be responsible for the recurrence of cancer which makes the patient return to the clinic with metastatic tumor tissue. Hence, the dysregulation of epigenetic machinery represents potential new therapeutic targets. Therefore, compounds with epigenetic activities have become crucial for developing new therapy regimens (e.g., antimetastatic agents) in the fight against cancer. Here, we review the epigenetic modifiers that have already been used in the clinic and/or in clinical trials, related preclinical studies in cancer therapy, and the smart combination strategies that target cancer stem cells along with the other cancer cells. The emerging role of epitranscriptome (RNA epigenetic) in cancer therapy has also been included in this review as a new avenue and potential target for the better management of cancer-beneficial epigenetic machinery.
表观遗传重编程在肿瘤发生及肿瘤特异性基因表达的维持中发挥着关键作用，这一过程尤其通过DNA甲基化和/或组蛋白修饰来实现。其机制明确。已知DNA甲基化模式的改变和/或特定组蛋白乙酰化/甲基化标记的缺失与癌症的几个特征相关，如耐药性、干性、上皮-间质转化和转移。最近还强调，表观遗传改变对于癌细胞（肿瘤起始细胞；癌症干细胞）的干细胞样特性的调节至关重要。癌症干细胞被认为是癌症复发的原因，这使得患者因转移性肿瘤组织而复诊。因此，表观遗传机制的失调代表了潜在的新治疗靶点。所以，具有表观遗传活性的化合物对于开发对抗癌症的新治疗方案（如抗转移药物）至关重要。在此，我们综述了已在临床和/或临床试验中使用的表观遗传修饰剂、癌症治疗相关的临床前研究，以及针对癌症干细胞和其他癌细胞的智能联合策略。作为更好管理癌症有益表观遗传机制的新途径和潜在靶点，表观转录组（RNA表观遗传）在癌症治疗中的新兴作用也已纳入本综述。
