Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Gynecol Oncol. 2010 Feb;116(2):195-201. doi: 10.1016/j.ygyno.2009.09.043. Epub 2009 Oct 24.
Epigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising preclinical studies, DNA methylation inhibitors in combination with existing chemotherapeutic agents have the potential for overcoming acquired drug resistance, laying the foundation for this specific class of epigenetic drug in ovarian cancer clinical trials. The recent completion of phase I trials of decitabine has yielded important information on dosing schedules and biological endpoints for evaluating patient responses. In addition, epigenetic drug effects on pharmacodyamic targets are beginning to emerge, and predictive epigenetic biomarkers and next generation epigenome therapeutics are being developed for application in clinical settings for ovarian cancer patients.
表观遗传学药物已被证明可以增强卵巢癌细胞系和动物模型中的基因表达和药物敏感性。基于有前景的临床前研究，DNA 甲基化抑制剂与现有的化疗药物联合使用有可能克服获得性耐药性，为这一特定类别的表观遗传学药物在卵巢癌临床试验中奠定了基础。最近完成的地西他滨 I 期临床试验为评估患者反应的剂量方案和生物学终点提供了重要信息。此外，表观遗传学药物对药效学靶点的影响开始显现，预测性表观遗传生物标志物和下一代表观基因组治疗药物正在开发中，以便在卵巢癌患者的临床环境中应用。
