Mammalian SWI/SNF Complexes in Cancer: Emerging Therapeutic Opportunities

Curr Opin Genet Dev. 2017 Feb;42:56-67. doi: 10.1016/j.gde.2017.02.004. Epub 2017 Apr 6.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone / genetics*
  • Humans
  • Mammals
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors