Department of Oncology, IRDB, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UK.
Ther Adv Med Oncol. 2010 Sep;2(5):319-29. doi: 10.1177/1758834010375759.
Epigenetic changes in tumours are associated not only with cancer development and progression, but also with resistance to chemotherapy. Aberrant DNA methylation at CpG islands and associated epigenetic silencing are observed during the acquisition of drug resistance. However, it remains unclear whether all of the observed changes are drivers of drug resistance, causally associated with response of tumours to chemotherapy, or are passenger events representing chance DNA methylation changes. Systematic approaches that link DNA methylation and expression with chemosensitivity will be required to identify key drivers. Such drivers will be important prognostic or predicitive biomarkers, both to existing chemotherapies, but also to epigenetic therapies used to modulate drug resistance.
肿瘤中的表观遗传改变不仅与癌症的发生和发展有关，还与化疗耐药性有关。在获得耐药性时，观察到 CpG 岛的异常 DNA 甲基化和相关的表观遗传沉默。然而，目前尚不清楚所有观察到的变化是否都是耐药性的驱动因素，是否与肿瘤对化疗的反应有因果关系，或者是否是代表随机 DNA 甲基化变化的乘客事件。需要采用系统的方法将 DNA 甲基化与表达与化疗敏感性联系起来，以确定关键的驱动因素。这些驱动因素将是重要的预后或预测生物标志物，不仅对现有的化疗药物，而且对用于调节耐药性的表观遗传治疗药物也很重要。
