Targeting ARID1A mutations in cancer. Cancer Treat Rev 2021 Nov;100:102287
Date
10/08/2021Pubmed ID
34619527DOI
10.1016/j.ctrv.2021.102287Scopus ID
2-s2.0-85116342891 (requires institutional sign-in at Scopus site) 136 CitationsAbstract
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.
Author List
Mullen J, Kato S, Sicklick JK, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDNA-Binding Proteins
Enzyme Inhibitors
Humans
Molecular Targeted Therapy
Mutation
Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
Transcription Factors
