title: Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities.
abstract: Mammalian SWI/SNF (BAF) chromatin remodeling complexes orchestrate a diverse set of chromatin alterations which impact transcriptional output. Recent whole-exome sequencing efforts have revealed that the genes encoding subunits of mSWI/SNF complexes are mutated in over 20% of cancers, spanning a wide range of tissue types. The majority of mutations result in loss of subunit protein expression, implicating mSWI/SNF subunits as tumor suppressors. mSWI/SNF-deficient cancers remain a therapeutic challenge, owing to a lack of potent and selective agents which target complexes or unique pathway dependencies generated by mSWI/SNF subunit perturbations. Here, we review the current landscape of mechanistic insights and emerging therapeutic opportunities for human malignancies driven by mSWI/SNF complex perturbation.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Chemical Biology Program, Harvard University, USA.
authors.forename: Roodolph
authors.initials: R
authors.lastname: St Pierre
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: Cigall_kadoch@dfci.harvard.edu.
authors.forename: Cigall
authors.initials: C
authors.lastname: Kadoch
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008322:Mammals; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors