Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy

  • Multi-subunit ATPase-dependent chromatin remodelling complexes SWI/SNF (switch/sucrose non-fermentable) are fundamental epigenetic regulators of gene transcription. Functional genomic studies revealed a remarkable mutation prevalence of SWI/SNF-encoding genes in 20–25% of all human cancers, frequently driving oncogenic programmes. Some SWI/SNF-mutant cancers are hypersensitive to perturbations in other SWI/SNF subunits, regulatory proteins and distinct biological pathways, often resulting in sustained anticancer effects and synthetic lethal interactions. Exploiting these vulnerabilities is a promising therapeutic strategy. Here, we review the importance of SWI/SNF chromatin remodellers in gene regulation as well as mechanisms leading to assembly defects and their role in cancer development. We will focus in particular on emerging strategies for the targeted therapy of SWI/SNF-deficient cancers using chemical probes, including proteolysis targeting chimeras, to induce synthetic lethality.

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Author:Marek WaniorORCiDGND, Andreas KrämerORCiDGND, Stefan KnappORCiD, Andreas C. JörgerORCiDGND
Parent Title (English):Oncogene
Publisher:Springer Nature
Place of publication:London
Document Type:Article
Date of Publication (online):2021/05/03
Date of first Publication:2021/05/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/08/03
Page Number:18
First Page:3637
Last Page:3654
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0