AUTHOR=Cheng Xuan , Zhao Jian-Xiong , Dong Feng , Cao Xu-Chen 

TITLE=ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.759577

DOI=10.3389/fonc.2021.759577

ISSN=2234-943X

ABSTRACT=<p>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, <italic>ARID1A</italic> is the most prevalent mutation of the SWI/SNF complex, which regulates DNA repair, recombination, and gene transcription. The low expression of <italic>ARID1A</italic> is associated with poor disease-free survival and overall survival of patients with luminal A or HER2-rich breast cancer. In addition, <italic>ARID1A</italic> 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 <italic>ARID1A</italic> alterations encourage us to explore new approaches to cope with <italic>ARID1A</italic> 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.</p>