ArticleJCI insight2022
ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 62 citations in OpenAlex.
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- ARID1A loss drives gastric signet ring cell carcinoma by regulating mucin production and secretion.Nature communications · 2026Article
- Ferroptosis as a therapeutic vulnerability in ARID1A-deficient bladder cancer.Communications biology · 2026Article
- Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.Signal transduction and targeted therapy · 2026Article
- Implications for clinical prognosis and target discovery of the SWI/SNF complex in genitourinary tumors.Discover oncology · 2026Review
- Inhibition of PRMT5 triggers synthetic lethality in ARID1A-deficient endometrial cancer by promoting aberrant R-loop accumulation.Molecular cancer · 2026Article
- Targeting WEE1 in ARID1A/TP53 Concurrent Mutant Colorectal Cancer by Exploiting R-Loop Accumulation and DNA Repair Deficiencies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of Selected Genes Associated With the Prediction of Prognosis in Bladder Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- A Review of ARID1A's Role in Breast Cancer Progression: Context-Dependent Mechanisms and Therapeutic Implications.Cancers · 2025Review
- MAP4 phosphorylation induced by ARID1A loss sensitizes colorectal cancer cells to EMP.Cell death & disease · 2025Article
- Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal-like and malignant urothelial cells.Molecular oncology · 2025Article
- Establishment of novel cholangiocarcinoma cell lines with ARID1A deficiency and preclinical validation of synthetic lethality therapies.Scientific reports · 2025Article
- ARID1A Loss plus CD8+ T-Cell Infiltration Associate with Favorable Clinical Outcomes in Urothelial Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Epigenetic synthetic lethality as a cancer therapeutic strategy: synergy of experimental and computational approaches.Epigenomics · 2025Review
- Targeting WEE1 to Overcome ARID1A Mutation-Driven Osimertinib Resistance in EGFR-Mutant Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Article
- Molecular interplay of ARID1A in gastrointestinal cancers.Medical oncology (Northwood, London, England) · 2025Review
- The role and mechanism of ARID1A in immunotherapy of gastric cancer.Clinical and experimental medicine · 2025Article
- Review
- Arid1a deficiency sensitises pancreatic cancer to fatty acid synthase inhibition.Clinical and translational medicine · 2025Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
Metastatic urothelial carcinoma is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, with ARID1A-inactivating mutations present in about 20% of tumors. EZH2, a histone methyltransferase, acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling is activated in more than 20% of bladder cancers. Using a combination of in vitro and in vivo data, including patient-derived xenografts, we show that ARID1A-mutant tumors were more sensitive to EZH2 inhibition than ARID1A WT tumors. Mechanistic studies revealed that (a) ARID1A deficiency results in a dependency on PI3K/AKT/mTOR signaling via upregulation of a noncanonical PI3K regulatory subunit, PIK3R3, and downregulation of MAPK signaling and (b) EZH2 inhibitor sensitivity is due to upregulation of PIK3IP1, a protein inhibitor of PI3K signaling. We show that PIK3IP1 inhibited PI3K signaling by inducing proteasomal degradation of PIK3R3. Furthermore, ARID1A-deficient bladder cancer was sensitive to combination therapies with EZH2 and PI3K inhibitors in a synergistic manner. Thus, our studies suggest that bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K and revealed mechanistic insights into the role of noncanonical PI3K constituents in bladder cancer biology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.