title: A rationale to target the SWI/SNF complex for cancer therapy.
abstract: SWI/SNF is a multisubunit chromatin-remodeling complex that performs fundamental roles in gene regulation, cell lineage specification, and organismal development. Mutations that inactivate SWI/SNF subunits are found in nearly 20% of human cancers, which indicates that the proper functioning of this complex is necessary to prevent tumor formation in diverse tissues. Recent studies show that SWI/SNF-mutant cancers depend on residual SWI/SNF complexes for their aberrant growth, thus revealing synthetic lethal interactions that could be exploited for therapeutic purposes. Other studies reveal that certain acute leukemias and small cell lung cancers, which lack SWI/SNF mutations, can be vulnerable to inhibition of the SWI/SNF ATPase subunit BRG1, whereas several normal and malignant cell types do not show this sensitivity. Here, we review the emerging evidence that implicates SWI/SNF as a tumor-dependency and candidate drug target in human cancer.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Anja F
authors.initials: AF
authors.lastname: Hohmann
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address: vakoc@cshl.edu.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Vakoc
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors
keywords: SWI/SNF; cancer therapy; synthetic lethality