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Targeting ARID1A mutations in cancer

Jaren Mullen1, Shumei Kato1, Jason K Sicklick2

  • 1Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.

Cancer Treatment Reviews
|October 7, 2021
PubMed

Insights

Mutations in the ARID1A gene, a key component of the SWI/SNF complex, are common in cancers like ovarian clear cell and uterine endometrioid types. These alterations impact gene expression and suggest potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The SWI/SNF chromatin remodeling complex is frequently altered in human cancers, with ARID1A being the most commonly mutated subunit.
  • ARID1A gene alterations lead to loss of function and are observed in approximately 6% of all cancers, notably ovarian clear cell (45%) and uterine endometrioid (37%) cancers.

Purpose of the Study:

  • To review the critical role of ARID1A in gene expression regulation relevant to oncogenesis and tumor suppression.
  • To identify potential therapeutic strategies and drug targets for ARID1A-altered cancers.

Main Methods:

  • Literature review and analysis of existing data on ARID1A mutations and their functional consequences.
  • Examination of ARID1A's involvement in key cellular pathways and its implications for cancer treatment.

Main Results:

  • ARID1A mutations affect critical pathways including PI3K/AKT/mTOR, immune response, EZH2 activity, and DNA damage response.
  • ARID1A alterations are associated with resistance to platinum chemotherapy and endocrine therapies.

Conclusions:

  • Targeting pathways regulated by ARID1A, such as mTOR and EZH2, and utilizing immune checkpoint blockade may benefit patients with ARID1A-altered cancers.
  • Understanding ARID1A's role is crucial for developing novel therapeutic approaches and overcoming treatment resistance.
Keywords:
ARID1AChromatin remodelingSWI/SNF

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