The BRG1/BRM associated factors (BAF) complex is a chromatin remodeling SWI/SNF which is mutated in 20% of cancers. This complex has many interchangeable subunits which may have oncogenic or tumor suppressor activity in a context-dependent manner. The BAF complex is mutated in 35-50% of metastatic prostate cancer (PC); however, its role in advanced disease is unclear. This review attempts to consolidate current knowledge of the BAF complex in PC and explore potential therapeutic approaches.
This review covers the known roles of some BAF subunits, their alterations, and the models which best explain their mechanisms in driving PC. Following this, the authors provide their expert perspective on how this complex could be targeted in the future with a personalized medicine approach.
Personalized medicine would allow for patient stratification to exploit synthetic lethal strategies in targeting a mutated BAF complex as shown experimentally in other cancers. BAF dependency can also be targeted in patients stratified for other molecular markers such as BRG1 targeting in phosphatase and tensin homolog (PTEN) deficient PC.
Expert opinion on drug discovery. 2020 Sep 16 [Epub ahead of print]
Andrew Hartley, Hing Y Leung, Imran Ahmad
Urology Research Group, CRUK Beatson Institute , Glasgow, UK.