Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors
The bromodomain and extra-terminal domain (BET) family inhibitors are small molecules that target the dysregulated epigenetic readers, BRD2, BRD3, BRD4 and BRDT, at various transcription-related sites, including super-enhancers. BET inhibitors are currently under investigation both in pre-clinical c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12669 |
| _version_ | 1797584515831431168 |
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| author | Ahmed M. Elshazly David A. Gewirtz |
| author_facet | Ahmed M. Elshazly David A. Gewirtz |
| author_sort | Ahmed M. Elshazly |
| collection | DOAJ |
| description | The bromodomain and extra-terminal domain (BET) family inhibitors are small molecules that target the dysregulated epigenetic readers, BRD2, BRD3, BRD4 and BRDT, at various transcription-related sites, including super-enhancers. BET inhibitors are currently under investigation both in pre-clinical cell culture and tumor-bearing animal models, as well as in clinical trials. However, as is the case with other chemotherapeutic modalities, the development of resistance is likely to constrain the therapeutic benefits of this strategy. One tumor cell survival mechanism that has been studied for decades is autophagy. Although four different functions of autophagy have been identified in the literature (cytoprotective, cytotoxic, cytostatic and non-protective), primarily the cytoprotective and cytotoxic forms appear to function in different experimental models exposed to BET inhibitors (with some evidence for the cytostatic form). This review provides an overview of the cytoprotective, cytotoxic and cytostatic functions of autophagy in response to BET inhibitors in various tumor models. Our aim is to determine whether autophagy targeting or modulation could represent an effective therapeutic strategy to enhance the response to these modalities and also potentially overcome resistance to BET inhibition. |
| first_indexed | 2024-03-10T23:52:49Z |
| format | Article |
| id | doaj.art-db01ec2c52b140df8e8a938f61558a59 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:49Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-db01ec2c52b140df8e8a938f61558a592023-11-19T01:27:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161266910.3390/ijms241612669Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET InhibitorsAhmed M. Elshazly0David A. Gewirtz1Department of Pharmacology and Toxicology, Massey Cancer Center, Virginia Commonwealth University, 401 College St., Richmond, VA 23298, USADepartment of Pharmacology and Toxicology, Massey Cancer Center, Virginia Commonwealth University, 401 College St., Richmond, VA 23298, USAThe bromodomain and extra-terminal domain (BET) family inhibitors are small molecules that target the dysregulated epigenetic readers, BRD2, BRD3, BRD4 and BRDT, at various transcription-related sites, including super-enhancers. BET inhibitors are currently under investigation both in pre-clinical cell culture and tumor-bearing animal models, as well as in clinical trials. However, as is the case with other chemotherapeutic modalities, the development of resistance is likely to constrain the therapeutic benefits of this strategy. One tumor cell survival mechanism that has been studied for decades is autophagy. Although four different functions of autophagy have been identified in the literature (cytoprotective, cytotoxic, cytostatic and non-protective), primarily the cytoprotective and cytotoxic forms appear to function in different experimental models exposed to BET inhibitors (with some evidence for the cytostatic form). This review provides an overview of the cytoprotective, cytotoxic and cytostatic functions of autophagy in response to BET inhibitors in various tumor models. Our aim is to determine whether autophagy targeting or modulation could represent an effective therapeutic strategy to enhance the response to these modalities and also potentially overcome resistance to BET inhibition.https://www.mdpi.com/1422-0067/24/16/12669autophagyBET familyBRD4senescencecytoprotectivecytotoxic |
| spellingShingle | Ahmed M. Elshazly David A. Gewirtz Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors International Journal of Molecular Sciences autophagy BET family BRD4 senescence cytoprotective cytotoxic |
| title | Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors |
| title_full | Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors |
| title_fullStr | Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors |
| title_full_unstemmed | Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors |
| title_short | Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors |
| title_sort | cytoprotective cytotoxic and cytostatic roles of autophagy in response to bet inhibitors |
| topic | autophagy BET family BRD4 senescence cytoprotective cytotoxic |
| url | https://www.mdpi.com/1422-0067/24/16/12669 |
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