Epigenetic Mechanisms and Therapeutic Targets in Chemoresistant High-Grade Serous Ovarian Cancer
High-grade serous ovarian cancer (HGSOC) is the most common ovarian cancer subtype, and the overall survival rate has not improved in the last three decades. Currently, most patients develop recurrent disease within 3 years and succumb to the disease within 5 years. This is an important area of rese...
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| Veröffentlicht in: | Cancers 2021-11, Vol.13 (23), p.5993 |
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| description | High-grade serous ovarian cancer (HGSOC) is the most common ovarian cancer subtype, and the overall survival rate has not improved in the last three decades. Currently, most patients develop recurrent disease within 3 years and succumb to the disease within 5 years. This is an important area of research, as the major obstacle to the treatment of HGSOC is the development of resistance to platinum chemotherapy. The cause of chemoresistance is still largely unknown and may be due to epigenetics modifications that are driving HGSOC metastasis and treatment resistance. The identification of epigenetic changes in chemoresistant HGSOC enables the development of epigenetic modulating drugs that may be used to improve outcomes. Several epigenetic modulating drugs have displayed promise as drug targets for HGSOC, such as demethylating agents azacitidine and decitabine. Others, such as histone deacetylase inhibitors and miRNA-targeting therapies, demonstrated promising preclinical results but resulted in off-target side effects in clinical trials. This article reviews the epigenetic modifications identified in chemoresistant HGSOC and clinical trials utilizing epigenetic therapies in HGSOC. |
| doi_str_mv | 10.3390/cancers13235993 |
| format | Article |
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Currently, most patients develop recurrent disease within 3 years and succumb to the disease within 5 years. This is an important area of research, as the major obstacle to the treatment of HGSOC is the development of resistance to platinum chemotherapy. The cause of chemoresistance is still largely unknown and may be due to epigenetics modifications that are driving HGSOC metastasis and treatment resistance. The identification of epigenetic changes in chemoresistant HGSOC enables the development of epigenetic modulating drugs that may be used to improve outcomes. Several epigenetic modulating drugs have displayed promise as drug targets for HGSOC, such as demethylating agents azacitidine and decitabine. Others, such as histone deacetylase inhibitors and miRNA-targeting therapies, demonstrated promising preclinical results but resulted in off-target side effects in clinical trials. 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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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This article reviews the epigenetic modifications identified in chemoresistant HGSOC and clinical trials utilizing epigenetic therapies in HGSOC.</description><subject>5-aza-2'-deoxycytidine</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Deacetylation</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Drug development</subject><subject>Epigenetics</subject><subject>Histone deacetylase</subject><subject>Metastases</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Nucleotide sequence</subject><subject>Ovarian cancer</subject><subject>Patients</subject><subject>Platinum</subject><subject>Review</subject><subject>Therapeutic targets</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkctLxDAQxoMoKurZa8GLl2qaNK-LIIsvUDy4nuOYTreRbbom7YL_vfGBqHOZgfnxzfcxhBxW9IRzQ08dBIcxVZxxYQzfILuMKlZKaerNX_MOOUjphebivFJSbZMdXmstKsp3ydPFyi8w4OhdcYeug-BTnwoITTHvMMIKp4_VHOICx1T4UMw67IeIyacRwlhc-0VXXkVosHjAOEypuF9D9JDBT3v7ZKuFZcKD775HHi8v5rPr8vb-6mZ2fls6bvRY8sY0WquaOaeewSlwUClNlWybljEla8UER9FKNCAMq2utKiF5LSTIHLLhe-TsS3c1PffYOAxjhKVdRd9DfLMDePt3E3xnF8PaainyWZkFjr8F4vA6YRpt75PD5RIC5liWSaoFr6kUGT36h74MUww53idFpZGGZer0i3JxSCli-2OmovbjgfbfA_k7oK-OSg</recordid><startdate>20211129</startdate><enddate>20211129</enddate><creator>Matthews, Bayley</creator><creator>Bowden, Nikola</creator><creator>Wong-Brown, Michelle</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2827-2852</orcidid><orcidid>https://orcid.org/0000-0002-6047-1694</orcidid></search><sort><creationdate>20211129</creationdate><title>Epigenetic Mechanisms and Therapeutic Targets in Chemoresistant High-Grade Serous Ovarian Cancer</title><author>Matthews, Bayley ; 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Currently, most patients develop recurrent disease within 3 years and succumb to the disease within 5 years. This is an important area of research, as the major obstacle to the treatment of HGSOC is the development of resistance to platinum chemotherapy. The cause of chemoresistance is still largely unknown and may be due to epigenetics modifications that are driving HGSOC metastasis and treatment resistance. The identification of epigenetic changes in chemoresistant HGSOC enables the development of epigenetic modulating drugs that may be used to improve outcomes. Several epigenetic modulating drugs have displayed promise as drug targets for HGSOC, such as demethylating agents azacitidine and decitabine. Others, such as histone deacetylase inhibitors and miRNA-targeting therapies, demonstrated promising preclinical results but resulted in off-target side effects in clinical trials. 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| subjects | 5-aza-2'-deoxycytidine Chemoresistance Chemotherapy Clinical trials Deacetylation Deoxyribonucleic acid DNA DNA methylation Drug development Epigenetics Histone deacetylase Metastases MicroRNAs miRNA Nucleotide sequence Ovarian cancer Patients Platinum Review Therapeutic targets |
| title | Epigenetic Mechanisms and Therapeutic Targets in Chemoresistant High-Grade Serous Ovarian Cancer |
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