title: A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex.
abstract: 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.
authors.affiliation: Microbiology, Tumour and Cell Biology (MTC), and Science for Life Laboratory (SciLifeLab), Karolinska Institutet, Tomtebodavägen 23A, Stockholm, 171 65, Sweden. giovanna.zinzalla@ki.se.
authors.forename: Giovanna
authors.identifier: http://orcid.org/0000-0002-1130-4865
authors.initials: G
authors.lastname: Zinzalla
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone
keywords: SWI/SNF complexes; cancer; epigenetics; transcription factors