{"doi":"10.1101/2021.01.12.426383","title":"ARID1A-mutant and deficient bladder cancer is sensitive to EZH2 pharmacologic inhibition","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Metastatic urothelial carcinoma of the bladder is generally incurable by current systemic therapy. Molecular characterization of bladder cancer (BLCa) has revealed multiple candidate driver genes for BLCa tumorigenesis. Epigenetic/chromatin modifiers have been shown to be frequently mutated in BLCa, with ARID1A mutations highly prevalent in nearly 20% of early and late stage tumors. EZH2 is a histone methyltransferase that acts as an oncogene. The data herein show that ARID1A deficient tumors, but not ARID1A wild-type tumors are sensitive to EZH2 inhibition. Specifically, EZH2 inhibitor-treated ARID1A deficient bladder cancer cells show significantly reduced cell viability, colony formation, and\n                  <jats:italic>in vivo</jats:italic>\n                  tumor growth relative to ARID1A-wild type bladder cancer cells. Thus, our study suggests that a specific subset of bladder cancer patients with ARID1A mutations can be therapeutically treated with pharmacologic inhibitors targeting EZH2.\n                </jats:p>","journal":null,"year":null,"id":593584,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":593496,"name":"Hasibur Rehman","orcid":"0000-0003-1551-6520","position":1,"is_corresponding":false},{"id":94253,"name":"Darshan S. Chandrashekar","orcid":"0000-0002-4295-9127","position":2,"is_corresponding":false},{"id":94258,"name":"Balabhadrapatruni V. S. K. Chakravarthi","orcid":"0000-0003-2761-9690","position":3,"is_corresponding":false},{"id":243863,"name":"Saroj Nepal","orcid":null,"position":4,"is_corresponding":false},{"id":1519226,"name":"Marie-Lisa Eich","orcid":null,"position":5,"is_corresponding":false},{"id":857947,"name":"Alyncia D. Robinson","orcid":"0000-0002-9369-7665","position":6,"is_corresponding":false},{"id":857946,"name":"Sumit Agarwal","orcid":"0000-0002-8305-3786","position":7,"is_corresponding":false},{"id":94255,"name":"Sai Akshaya Hodigere Balasubramanya","orcid":null,"position":8,"is_corresponding":false},{"id":61282,"name":"Gurudatta Naik","orcid":"0000-0001-7265-6605","position":9,"is_corresponding":false},{"id":298364,"name":"Upender Manne","orcid":"0000-0002-1545-3032","position":10,"is_corresponding":false},{"id":1519228,"name":"George J Netto","orcid":null,"position":11,"is_corresponding":false},{"id":381830,"name":"Chong-xian Pan","orcid":"0000-0002-8588-3994","position":12,"is_corresponding":false},{"id":274683,"name":"Guru Sonpavde","orcid":"0000-0002-1010-9611","position":13,"is_corresponding":false},{"id":64717,"name":"Sooryanarayana Varambally","orcid":"0000-0002-2277-1127","position":14,"is_corresponding":false},{"id":594872,"name":"James E. Ferguson","orcid":"0000-0001-9073-9615","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ARID1A-mutant and deficient bladder cancer is sensitive to EZH2 pharmacologic inhibition","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Metastatic urothelial carcinoma of the bladder is generally incurable by current systemic therapy. Molecular characterization of bladder cancer (BLCa) has revealed multiple candidate driver genes for BLCa tumorigenesis. Epigenetic/chromatin modifiers have been shown to be frequently mutated in BLCa, with ARID1A mutations highly prevalent in nearly 20% of early and late stage tumors. EZH2 is a histone methyltransferase that acts as an oncogene. The data herein show that ARID1A deficient tumors, but not ARID1A wild-type tumors are sensitive to EZH2 inhibition. Specifically, EZH2 inhibitor-treated ARID1A deficient bladder cancer cells show significantly reduced cell viability, colony formation, and\n                  <jats:italic>in vivo</jats:italic>\n                  tumor growth relative to ARID1A-wild type bladder cancer cells. Thus, our study suggests that a specific subset of bladder cancer patients with ARID1A mutations can be therapeutically treated with pharmacologic inhibitors targeting EZH2.\n                </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23304386","pmcid":null,"openalex_id":"https://openalex.org/W3119406774","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2022,"count":2}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/01/13/2021.01.12.426383.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/01/13/2021.01.12.426383.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2021.01.12.426383","host_type":"publisher"},{"url":"https://doi.org/10.1101/2021.01.12.426383","host_type":"repository"},{"url":"https://dx.doi.org/10.1101/2021.01.12.426383","host_type":""}],"fields_of_study":["Bladder and Urothelial Cancer Treatments","Epigenetics and DNA Methylation","Peptidase Inhibition and Analysis","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["ARID1A","EZH2","Cancer research","Bladder cancer","Carcinogenesis","Biology","Cancer","Epigenetics","Histone","Mutation","Gene","Genetics"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T11:32:56.748082Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}