Allen Andrew
Pharmion Corp, 1700 Owens Street, Suite 205, San Francisco, CA 94158, USA.
IDrugs. 2007 Oct;10(10):709-12.
Over the last two decades, preclinical and clinical research has implicated epigenetic alterations in the pathogenesis and progression of cancer. Epigenetic changes, involving both DNA methylation and alterations in chromatin structure, are associated with the inhibition of transcription of key cell regulatory genes that, under normal conditions, control the cell cycle and initiate apoptotic cell death in neoplastic cells. Drugs have been developed with functional effects, including DNA hypomethylation and histone acetylation, that serve to restore the normal transcription of cell regulatory genes (eg, tumor suppressor genes). DNA hypomethylating agents, such as azacitidine (Vidaza), and histone deacetylase inhibitors such as vorinostat (Zolinza) have been approved in the US for the treatment of cancer, reinforcing the importance of these pathways in the biology of this disease. Current research involves combining these classes of agents and identifying new drug targets within the growing family of epigenetic enzymes.
在过去二十年中，临床前和临床研究表明表观遗传改变与癌症的发病机制和进展有关。表观遗传变化，包括DNA甲基化和染色质结构改变，与关键细胞调节基因转录的抑制有关，这些基因在正常情况下控制细胞周期并引发肿瘤细胞的凋亡性细胞死亡。已开发出具有功能效应的药物，包括DNA低甲基化和组蛋白乙酰化，用于恢复细胞调节基因（如肿瘤抑制基因）的正常转录。DNA低甲基化剂，如阿扎胞苷（Vidaza），以及组蛋白脱乙酰酶抑制剂，如伏立诺他（Zolinza），已在美国被批准用于治疗癌症，这强化了这些途径在该疾病生物学中的重要性。当前的研究包括将这些类别的药物联合使用，并在不断增加的表观遗传酶家族中确定新的药物靶点。
