Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy
Histone deacetylation inhibitors (HDACi) offer high potential for future cancer therapy as they can re-establish the expression of epigenetically silenced cell death programs. HDACi-induced autophagy offers the possibility to counteract the frequently present apoptosis-resistance as well as stress c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/1/109 |
| _version_ | 1797725905128259584 |
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| author | Maria Mrakovcic Leopold F. Fröhlich |
| author_facet | Maria Mrakovcic Leopold F. Fröhlich |
| author_sort | Maria Mrakovcic |
| collection | DOAJ |
| description | Histone deacetylation inhibitors (HDACi) offer high potential for future cancer therapy as they can re-establish the expression of epigenetically silenced cell death programs. HDACi-induced autophagy offers the possibility to counteract the frequently present apoptosis-resistance as well as stress conditions of cancer cells. Opposed to the function of apoptosis and necrosis however, autophagy activated in cancer cells can engage in a tumor-suppressive or tumor-promoting manner depending on mostly unclarified factors. As a physiological adaption to apoptosis resistance in early phases of tumorigenesis, autophagy seems to resume a tumorsuppressive role that confines tumor necrosis and inflammation or even induces cell death in malignant cells. During later stages of tumor development, chemotherapeutic drug-induced autophagy seems to be reprogrammed by the cancer cell to prevent its elimination and support tumor progression. Consistently, HDACi-mediated activation of autophagy seems to exert a protective function that prevents the induction of apoptotic or necrotic cell death in cancer cells. Thus, resistance to HDACi-induced cell death is often encountered in various types of cancer as well. The current review highlights the different mechanisms of HDACi-elicited autophagy and corresponding possible molecular determinants of therapeutic resistance in cancer. |
| first_indexed | 2024-03-12T10:38:02Z |
| format | Article |
| id | doaj.art-ca7557a6a48a432fb2cca1f4f62b4aff |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T10:38:02Z |
| publishDate | 2019-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ca7557a6a48a432fb2cca1f4f62b4aff2023-09-02T08:29:18ZengMDPI AGCancers2072-66942019-12-0112110910.3390/cancers12010109cancers12010109Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced AutophagyMaria Mrakovcic0Leopold F. Fröhlich1Department of Cranio-Maxillofacial Surgery, University of Münster, 48149 Münster, GermanyDepartment of Cranio-Maxillofacial Surgery, University of Münster, 48149 Münster, GermanyHistone deacetylation inhibitors (HDACi) offer high potential for future cancer therapy as they can re-establish the expression of epigenetically silenced cell death programs. HDACi-induced autophagy offers the possibility to counteract the frequently present apoptosis-resistance as well as stress conditions of cancer cells. Opposed to the function of apoptosis and necrosis however, autophagy activated in cancer cells can engage in a tumor-suppressive or tumor-promoting manner depending on mostly unclarified factors. As a physiological adaption to apoptosis resistance in early phases of tumorigenesis, autophagy seems to resume a tumorsuppressive role that confines tumor necrosis and inflammation or even induces cell death in malignant cells. During later stages of tumor development, chemotherapeutic drug-induced autophagy seems to be reprogrammed by the cancer cell to prevent its elimination and support tumor progression. Consistently, HDACi-mediated activation of autophagy seems to exert a protective function that prevents the induction of apoptotic or necrotic cell death in cancer cells. Thus, resistance to HDACi-induced cell death is often encountered in various types of cancer as well. The current review highlights the different mechanisms of HDACi-elicited autophagy and corresponding possible molecular determinants of therapeutic resistance in cancer.https://www.mdpi.com/2072-6694/12/1/109histone deacetylase inhibitorhdacidrug resistanceautophagycell deathcancertumorchemotherapyradiotherapy |
| spellingShingle | Maria Mrakovcic Leopold F. Fröhlich Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy Cancers histone deacetylase inhibitor hdaci drug resistance autophagy cell death cancer tumor chemotherapy radiotherapy |
| title | Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy |
| title_full | Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy |
| title_fullStr | Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy |
| title_full_unstemmed | Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy |
| title_short | Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy |
| title_sort | molecular determinants of cancer therapy resistance to hdac inhibitor induced autophagy |
| topic | histone deacetylase inhibitor hdaci drug resistance autophagy cell death cancer tumor chemotherapy radiotherapy |
| url | https://www.mdpi.com/2072-6694/12/1/109 |
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