Frontiers in Oncology (Nov 2021)

ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

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

DOI
https://doi.org/10.3389/fonc.2021.759577
Journal volume & issue
Vol. 11

Abstract

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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