Borley Jane, Brown Robert
a Department of Surgery and Cancer , Imperial College London, Hammersmith Hospital , London W12 0NN , UK.
Ann Med. 2015;47(5):359-69. doi: 10.3109/07853890.2015.1043140. Epub 2015 Jul 10.
Epithelial ovarian cancer is the most lethal gynaecological cancer with the majority of patients succumbing to chemotherapy-resistant disease. Unravelling the mechanisms of drug resistance and how it can be prevented or reversed is a pivotal challenge in the treatment of cancer. Epigenetic mechanisms appear to play a crucial role in the development of inherent and acquired resistance in ovarian cancer. Aberrant epigenetic states can be reversed by drug therapy, and thus maintenance of epigenetic change is a potential target to halt or reverse chemotherapy resistance. This review explores the evidence that demonstrates that DNA methylation, histone modification, and microRNAs are associated with inherent and acquired chemotherapy resistance in ovarian cancer and the current challenges associated with this. We also explore current epigenetic therapies used in patients with drug-resistant ovarian cancer and future potential targets.
上皮性卵巢癌是最致命的妇科癌症,大多数患者死于化疗耐药性疾病。阐明耐药机制以及如何预防或逆转耐药性是癌症治疗中的关键挑战。表观遗传机制似乎在卵巢癌固有耐药性和获得性耐药性的发展中起着至关重要的作用。异常的表观遗传状态可以通过药物治疗逆转,因此维持表观遗传变化是阻止或逆转化疗耐药性的一个潜在靶点。本综述探讨了表明DNA甲基化、组蛋白修饰和微小RNA与卵巢癌固有和获得性化疗耐药性相关的证据以及与此相关的当前挑战。我们还探讨了目前用于耐药性卵巢癌患者的表观遗传疗法以及未来的潜在靶点。