Exploiting epigenetic vulnerabilities in solid tumors: Novel therapeutic opportunities in the treatment of SWI/SNF-defective cancers

Roman M. Chabanon, Daphné Morel, Sophie Postel-Vinay

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)

Abstract

Mammalian switch/sucrose non-fermentable (mSWI/SNF) family complexes are pivotal elements of the chromatin remodeling machinery, which contribute to the regulation of several major cellular functions. Large-scale exome-wide sequencing studies have identified mutations in genes encoding mSWI/SNF subunits in 20% of all human cancers, establishing mSWI/SNF deficiency as a recurrent oncogenic alteration. Accumulating evidence now supports that several mSWI/SNF defects represent targetable vulnerabilities in cancer; notably, recent research advances have unveiled unexpected synthetic lethal opportunities that foster the development of novel biomarker-driven and mechanism-based therapeutic approaches for the treatment of mSWI/SNF-deficient tumors. Here, we review the latest breakthroughs and discoveries that inform our understanding of the mSWI/SNF complexes biology in carcinogenesis, and discuss the most promising therapeutic strategies to target mSWI/SNF defects in human solid malignancies.

Original languageEnglish
Pages (from-to)180-198
Number of pages19
JournalSeminars in Cancer Biology
Volume61
DOIs
Publication statusPublished - 1 Apr 2020
Externally publishedYes

Keywords

  • Epigenetic vulnerabilities
  • Mechanism-based therapeutic strategies
  • Molecular biomarkers
  • Synthetic lethality
  • mSWI/SNF complexes

Cite this