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A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex
Author(s) -
Zinzalla Giovanna
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500565
Subject(s) - drug discovery , swi/snf , chromatin , chromatin remodeling , drug , cancer , computational biology , chemistry , drug target , biology , microbiology and biotechnology , cancer research , genetics , biochemistry , pharmacology , dna
Mutations in subunits of the SWI/SNF chromatin remodelling complex are found in 20 % of human cancers. At face value, this would appear to indicate that this multiprotein complex is a potent tumour suppressor. However, it has recently emerged that some mutations in the SWI/SNF complex can have a gain‐of‐function effect and that in other tumours, such as pancreatic cancer, leukaemia, and breast cancer, the wild‐type complex is used to drive cancer. Thus, paradoxically, this “tumour suppressor” has become an attractive target for developing anticancer agents. The SWI/SNF complex makes several protein–protein interactions both within the complex and with a wide range of transcription factors, and targeting these protein–protein interactions is emerging as the best approach to modulating the activity of the complex selectively.