Vulnerabilities of Mutant SWI/SNF Complexes in Cancer

• Published in: Cancer cell 2014-09, Vol.26 (3), p.309-317
• Main Authors: Helming, Katherine C., Wang, Xiaofeng, Roberts, Charles W.M.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Genetic Predisposition to Disease; Humans; Molecular Targeted Therapy; Multiprotein Complexes - genetics; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Protein Subunits - genetics; Transcription Factors - genetics
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2014.07.018

Cancer genome sequencing efforts have revealed the novel theme that chromatin modifiers are frequently mutated across a wide spectrum of cancers. Mutations in genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are particularly prevalent, occurring in 20% of all human cancers. As these are typically loss-of-function mutations and not directly therapeutically targetable, central goals have been to elucidate mechanism and identify vulnerabilities created by these mutations. Here, we discuss emerging data that these mutations lead to the formation of aberrant residual SWI/SNF complexes that constitute a specific vulnerability and discuss the potential for exploiting these dependencies in SWI/SNF mutant cancers.