title: Epigenetic mechanisms and therapeutic targets of chemotherapy resistance in epithelial ovarian cancer.
abstract: 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.
authors.affiliation: a Department of Surgery and Cancer , Imperial College London, Hammersmith Hospital , London W12 0NN , UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Borley
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000737:chemistry; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D035683:MicroRNAs
keywords: Chemotherapy resistance; DNA methylation; epigenetics; histone modification; microRNA; ovarian cancer