TY - JOUR TI - Exploiting epigenetic dependencies in ovarian cancer therapy AU - Coughlan, Aisling Y. AU - Testa, Giuseppe T2 - International Journal of Cancer AB - Ovarian cancer therapy has remained fundamentally unchanged for 50 years, with surgery and chemotherapy still the frontline treatments. Typically asymptomatic until advanced stages, ovarian cancer is known as ‘the silent killer’. Consequently, it has one of the worst 5-year survival rates, as low as 30%. The most frequent driver mutations are found in well-defined tumor suppressors, such as p53 and BRCA1/2. In recent years it has become clear that, like the majority of other cancers, many epigenetic regulators are altered in ovarian cancer, including EZH2, SMARCA2/4 and ARID1A. Disruption of epigenetic regulators often leads to loss of transcriptional control, aberrant cell fate trajectories and disruption of senescence, apoptotic and proliferation pathways. These mitotically-inherited epigenetic alterations are particularly promising targets for therapy as they are largely reversible. Consequently, many drugs targeting chromatin modifiers and other epigenetic regulators are at various stages of clinical trials for other cancers. Understanding the mechanisms by which ovarian cancer-specific epigenetic processes are disrupted in patients can allow for informed targeting of epigenetic pathways tailored for each patient. In recent years, there have been groundbreaking new advances in disease modelling through ovarian cancer organoids; these models, alongside single-cell transcriptomic and epigenomic technologies, allow the elucidation of the epigenetic pathways deregulated in ovarian cancer. As a result, ovarian cancer therapy may finally be ready to advance to next-generation treatments. Here, we review the major developments in ovarian cancer, including genetics, model systems and technologies available for their study and the implications of applying epigenetic therapies to ovarian cancer. This article is protected by copyright. All rights reserved. DO - 10.1002/ijc.33727 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1097-0215 UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.33727 Y2 - 2021/07/15/17:31:52 KW - Ovarian cancer KW - chromatin remodeling KW - disease modelling KW - epigenetic drugs KW - precision oncology ER -