TY  - JOUR
A1  - Wanior, Marek
A1  - Krämer, Andreas
A1  - Knapp, Stefan
A1  - Jörger, Andreas C.
T1  - Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy
T2  - Oncogene
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62385
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-623858
SN  - 1476-5594
VL  - 40
SP  - 3637
EP  - 3654
PB  - Springer Nature
CY  - London
ER  -