Therapeutic significance of ARID1A mutation in bladder cancer

Abstract

Bladder cancer (BC) develops from the tissues of the urinary bladder and is responsible for nearly 200,000 deaths annually. This review aims to integrate knowledge of recently discovered functions of the chromatin remodelling tumour suppressor protein ARID1A in bladder urothelial carcinoma with a focus on highlighting potential new avenues for the development of personalised therapies for ARID1A mutant bladder tumours. ARID1A is a component of the SWI/SNF chromatin remodelling complex and functions to control many important biological processes such as transcriptional regulation, DNA damage repair (DDR), cell cycle control, regulation of the tumour microenvironment and anti-cancer immunity. ARID1A mutation is emerging as a truncal driver mutation that underlies the development of a sub-set of urothelial carcinomas, in cooperation with other driver mutations, to cause dysregulation of a number of key cellular processes. These processes represent tumour drivers but also represent potentially attractive therapeutic targets.

Keywords

• Bladder cancer
• ARID1A
• Synthetic lethalities
• Immune checkpoint therapy
• Clonal expansions