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Exploiting epigenetic dependencies in ovarian cancer therapy

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...

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Autores principales: Coughlan, Aisling Y., Testa, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292863/
https://www.ncbi.nlm.nih.gov/pubmed/34213777
http://dx.doi.org/10.1002/ijc.33727
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author Coughlan, Aisling Y.
Testa, Giuseppe
author_facet Coughlan, Aisling Y.
Testa, Giuseppe
author_sort Coughlan, Aisling Y.
collection PubMed
description 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 modeling 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.
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spelling pubmed-92928632022-07-20 Exploiting epigenetic dependencies in ovarian cancer therapy Coughlan, Aisling Y. Testa, Giuseppe Int J Cancer Review 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 modeling 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. John Wiley & Sons, Inc. 2021-08-06 2021-11-15 /pmc/articles/PMC9292863/ /pubmed/34213777 http://dx.doi.org/10.1002/ijc.33727 Text en © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Coughlan, Aisling Y.
Testa, Giuseppe
Exploiting epigenetic dependencies in ovarian cancer therapy
title Exploiting epigenetic dependencies in ovarian cancer therapy
title_full Exploiting epigenetic dependencies in ovarian cancer therapy
title_fullStr Exploiting epigenetic dependencies in ovarian cancer therapy
title_full_unstemmed Exploiting epigenetic dependencies in ovarian cancer therapy
title_short Exploiting epigenetic dependencies in ovarian cancer therapy
title_sort exploiting epigenetic dependencies in ovarian cancer therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292863/
https://www.ncbi.nlm.nih.gov/pubmed/34213777
http://dx.doi.org/10.1002/ijc.33727
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