Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications
SWI/SNF enzymes are heterogeneous multi-subunit complexes that utilize the energy from ATP hydrolysis to remodel chromatin structure, facilitating transcription, DNA replication, and repair. In mammalian cells, distinct sub-complexes, including cBAF, ncBAF, and PBAF exhibit varying subunit compositi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Epigenomes |
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| Online Access: | https://www.mdpi.com/2075-4655/8/1/7 |
| _version_ | 1797241139366985728 |
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| author | Megan R. Dreier Jasmine Walia Ivana L. de la Serna |
| author_facet | Megan R. Dreier Jasmine Walia Ivana L. de la Serna |
| author_sort | Megan R. Dreier |
| collection | DOAJ |
| description | SWI/SNF enzymes are heterogeneous multi-subunit complexes that utilize the energy from ATP hydrolysis to remodel chromatin structure, facilitating transcription, DNA replication, and repair. In mammalian cells, distinct sub-complexes, including cBAF, ncBAF, and PBAF exhibit varying subunit compositions and have different genomic functions. Alterations in the SWI/SNF complex and sub-complex functions are a prominent feature in cancer, making them attractive targets for therapeutic intervention. Current strategies in cancer therapeutics involve the use of pharmacological agents designed to bind and disrupt the activity of SWI/SNF complexes or specific sub-complexes. Inhibitors targeting the catalytic subunits, SMARCA4/2, and small molecules binding SWI/SNF bromodomains are the primary approaches for suppressing SWI/SNF function. Proteolysis-targeting chimeras (PROTACs) were generated by the covalent linkage of the bromodomain or ATPase-binding ligand to an E3 ligase-binding moiety. This engineered connection promotes the degradation of specific SWI/SNF subunits, enhancing and extending the impact of this pharmacological intervention in some cases. Extensive preclinical studies have underscored the therapeutic potential of these drugs across diverse cancer types. Encouragingly, some of these agents have progressed from preclinical research to clinical trials, indicating a promising stride toward the development of effective cancer therapeutics targeting SWI/SNF complex and sub-complex functions. |
| first_indexed | 2024-04-24T18:18:34Z |
| format | Article |
| id | doaj.art-eb21cf5abd944ab2a5649c4b3f358474 |
| institution | Directory Open Access Journal |
| issn | 2075-4655 |
| language | English |
| last_indexed | 2024-04-24T18:18:34Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Epigenomes |
| spelling | doaj.art-eb21cf5abd944ab2a5649c4b3f3584742024-03-27T13:37:51ZengMDPI AGEpigenomes2075-46552024-02-0181710.3390/epigenomes8010007Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and ImplicationsMegan R. Dreier0Jasmine Walia1Ivana L. de la Serna2Department of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Ave, Toledo 43614, OH, USADepartment of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Ave, Toledo 43614, OH, USADepartment of Cell and Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Ave, Toledo 43614, OH, USASWI/SNF enzymes are heterogeneous multi-subunit complexes that utilize the energy from ATP hydrolysis to remodel chromatin structure, facilitating transcription, DNA replication, and repair. In mammalian cells, distinct sub-complexes, including cBAF, ncBAF, and PBAF exhibit varying subunit compositions and have different genomic functions. Alterations in the SWI/SNF complex and sub-complex functions are a prominent feature in cancer, making them attractive targets for therapeutic intervention. Current strategies in cancer therapeutics involve the use of pharmacological agents designed to bind and disrupt the activity of SWI/SNF complexes or specific sub-complexes. Inhibitors targeting the catalytic subunits, SMARCA4/2, and small molecules binding SWI/SNF bromodomains are the primary approaches for suppressing SWI/SNF function. Proteolysis-targeting chimeras (PROTACs) were generated by the covalent linkage of the bromodomain or ATPase-binding ligand to an E3 ligase-binding moiety. This engineered connection promotes the degradation of specific SWI/SNF subunits, enhancing and extending the impact of this pharmacological intervention in some cases. Extensive preclinical studies have underscored the therapeutic potential of these drugs across diverse cancer types. Encouragingly, some of these agents have progressed from preclinical research to clinical trials, indicating a promising stride toward the development of effective cancer therapeutics targeting SWI/SNF complex and sub-complex functions.https://www.mdpi.com/2075-4655/8/1/7SWI/SNF chromatin-remodeling complexescancerallosteric ATPAse inhibitorsbromodomain inhibitorsPROTACsepigenetics |
| spellingShingle | Megan R. Dreier Jasmine Walia Ivana L. de la Serna Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications Epigenomes SWI/SNF chromatin-remodeling complexes cancer allosteric ATPAse inhibitors bromodomain inhibitors PROTACs epigenetics |
| title | Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications |
| title_full | Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications |
| title_fullStr | Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications |
| title_full_unstemmed | Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications |
| title_short | Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications |
| title_sort | targeting swi snf complexes in cancer pharmacological approaches and implications |
| topic | SWI/SNF chromatin-remodeling complexes cancer allosteric ATPAse inhibitors bromodomain inhibitors PROTACs epigenetics |
| url | https://www.mdpi.com/2075-4655/8/1/7 |
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