Targeting ARID1A mutations in cancer

Jaren Mullen; Shumei Kato; Jason K Sicklick; Razelle Kurzrock

doi:10.1016/j.ctrv.2021.102287

Targeting ARID1A mutations in cancer

Cancer Treat Rev. 2021 Nov:100:102287. doi: 10.1016/j.ctrv.2021.102287. Epub 2021 Sep 6.

Authors

Jaren Mullen¹, Shumei Kato², Jason K Sicklick³, Razelle Kurzrock⁴

Affiliations

¹ Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
² Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. Electronic address: smkato@health.ucsd.edu.
³ Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Surgery, Division of Surgical Oncology, UC San Diego School of Medicine, San Diego, CA, USA.
⁴ WIN Consortium for Personalized Cancer Therapy, USA.

PMID: 34619527
DOI: 10.1016/j.ctrv.2021.102287

Abstract

Genes encoding SWI/SNF chromatin remodeling complex subunits are collectively mutated in approximately 20% of human cancers. ARID1A is a SWI/SNF subunit gene whose protein product binds DNA. ARID1A gene alterations result in loss of function. It is the most commonly mutated member of the SWI/SNF complex, being aberrant in ∼6% of cancers overall, including ovarian clear cell cancers (∼45% of patients) and uterine endometrioid cancers (∼37%). ARID1A has a crucial role in regulating gene expression that drives oncogenesis or tumor suppression. In particular, ARID1A participates in control of the PI3K/AKT/mTOR pathway, immune responsiveness to cancer, EZH2 methyltransferase activity, steroid receptor modulation, DNA damage checkpoints, and regulation of p53 targets and KRAS signaling. A variety of compounds may be of benefit in ARID1A-altered cancers: immune checkpoint blockade, and inhibitors of mTOR, EZH2, histone deacetylases, ATR and/or PARP. ARID1A alterations may also mediate resistance to platinum chemotherapy and estrogen receptor degraders/modulators.

Keywords: ARID1A; Chromatin remodeling; SWI/SNF.

Publication types

Review

MeSH terms

Animals
DNA-Binding Proteins / genetics*
Enzyme Inhibitors / therapeutic use
Humans
Immune Checkpoint Inhibitors / therapeutic use
Molecular Targeted Therapy
Mutation*
Neoplasms / drug therapy*
Neoplasms / genetics
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
Transcription Factors / genetics*

Substances

ARID1A protein, human
Arid1a protein, mouse
DNA-Binding Proteins
Enzyme Inhibitors
Immune Checkpoint Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Transcription Factors