ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

Abstract

Distant metastasis is the principal cause of mortality for breast cancer patients. Targeting specific mutations that have been acquired during the evolution process of advanced breast cancer is a potential means of enhancing the clinical efficacy of treatment strategies. In metastatic breast cancer, ARID1A is the most prevalent mutation of the SWI/SNF complex, which regulates DNA repair, recombination, and gene transcription. The low expression of ARID1A is associated with poor disease-free survival and overall survival of patients with luminal A or HER2-rich breast cancer. In addition, ARID1A plays a prominent role in maintaining luminal characteristics and has an advantage for identifying responses to treatment, including endocrine therapies, HDAC inhibitors and CDK4/6 inhibitors. The therapeutic vulnerabilities initiated by ARID1A alterations encourage us to explore new approaches to cope with ARID1A mutant-related drug resistance or metastasis. In this review, we describe the mutation profiles of ARID1A in metastatic breast cancer and the structure and function of ARID1A and the SWI/SNF complex as well as discuss the potential mechanisms of ARID1A-mediated endocrine resistance and therapeutic potential.

Keywords: ARID1A; SWI/SNF complex; endocrine resistance; metastatic breast cancer; synthetic lethality; therapeutic targets.

Figure 1

ARID1A protein mutation in metastatic breast cancer. The mutations are colored by the type of mutations: missense, nonsense, silent, and inframe.

Figure 2

Potential treatments of ARID1A-mutated metastatic breast cancer. ARID1A mutation gives rise to specific signaling pathways and cellular functions. They are selected as therapeutic targets against ARID1A mutations.