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Targeting the BAF complex in advanced prostate cancer.

Andrew Hartley1, Hing Y Leung1,2, Imran Ahmad1,2

  • 1Urology Research Group, CRUK Beatson Institute , Glasgow, UK.

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The BRG1/BRM associated factors (BAF) complex, mutated in metastatic prostate cancer (PC), has unclear roles. This review consolidates BAF complex knowledge in PC and explores personalized therapeutic strategies.

Keywords:
ARID1ABAFProstateSWI/SNFcancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The BRG1/BRM associated factors (BAF) complex, a SWI/SNF chromatin remodeler, is frequently mutated in various cancers, including 35-50% of metastatic prostate cancer (PC).
  • The BAF complex comprises interchangeable subunits, some exhibiting context-dependent oncogenic or tumor suppressor activities, leading to an unclear role in advanced PC.
  • Understanding the specific BAF subunit alterations and their functional consequences is crucial for deciphering their role in prostate cancer progression.

Purpose of the Study:

  • To consolidate current knowledge regarding the BAF complex's role in prostate cancer.
  • To explore potential therapeutic strategies targeting the BAF complex in PC.
  • To provide an expert perspective on personalized medicine approaches for BAF-mutated prostate cancer.

Main Methods:

  • Review of existing literature on BAF complex subunits, their alterations, and mechanisms in prostate cancer.
  • Analysis of experimental models elucidating BAF complex function in PC.
  • Synthesis of expert opinion on future therapeutic targeting strategies.

Main Results:

  • The review details the known functions of specific BAF subunits and their alterations in driving PC.
  • It highlights the importance of context-dependent subunit activity in cancer development.
  • Experimental evidence suggests BAF dependency can be exploited therapeutically.

Conclusions:

  • Targeting the mutated BAF complex offers a promising avenue for prostate cancer treatment.
  • Personalized medicine approaches, including patient stratification, are essential for effective BAF-targeted therapies.
  • Synthetic lethal strategies and targeting BAF dependency in conjunction with other molecular markers (e.g., PTEN deficiency) show potential for BAF-mutated PC.