{"doi":"10.1021/acsptsci.5c00402","title":"A First-in-Class Chemical-Induced Proximity System Achieves Dose-Dependent Control of Tumor Protein P53 Gene Activation in Preclinical Models of Gastric Cancer","abstract":"High Resolution Image Download MS PowerPoint Slide The tumor protein P53 ( TP53 ) gene has long been studied in cancer research with genomic and epigenetic aberrations playing a driving role in cancer pathology, yet even after decades of work, only a few methods have been developed to specifically target TP53 therapeutically. Some cancers are driven by loss-of-function TP53 mutations, while others have wild-type TP53 in a transcriptionally repressed state; the latter is exploitable by advances in epigenome editing. In our previous work, we demonstrated that deactivated CRISPR/Cas9 systems (dCas9), combined with an FK-506-binding protein (FKBP) recruitment protein tag and chemical epigenetic modifier (CEM) small molecules, can elicit gene-specific changes in expression in a dose-dependent manner. Here, we describe the development, application, and characterization of the dCas9-FKBP-CEM technology to increase TP53 expression. We demonstrate that catalyzing increased TP53 expression via dCas9-FKBP-CEM87 induced apoptosis, cell cycle arrest, and tumor growth inhibition in a dose-dependent manner in preclinical models of gastric cancer.","journal":"ACS Pharmacology & Translational Science","year":2025,"id":574365,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1140015,"name":"Ryan M. Kemper","orcid":"0000-0002-5468-7827","position":1,"is_corresponding":false},{"id":644907,"name":"Anna M. Chiarella","orcid":"0000-0003-1224-9324","position":2,"is_corresponding":false},{"id":1482130,"name":"Stephany Gonzalez Tineo","orcid":null,"position":3,"is_corresponding":false},{"id":16703,"name":"Michael C. Carroll","orcid":"0000-0002-3213-4295","position":4,"is_corresponding":false},{"id":62826,"name":"Surya Tripathi","orcid":null,"position":5,"is_corresponding":false},{"id":149426,"name":"B. E. Clarke","orcid":null,"position":6,"is_corresponding":false},{"id":554099,"name":"Xufen Yu","orcid":"0000-0001-7794-7890","position":7,"is_corresponding":false},{"id":401433,"name":"Xiaoping Hu","orcid":"0000-0001-7014-5983","position":8,"is_corresponding":false},{"id":1482131,"name":"Aidan J. Cooke","orcid":null,"position":9,"is_corresponding":false},{"id":1482132,"name":"Bhavika C. Chirumamilla","orcid":null,"position":10,"is_corresponding":false},{"id":1482133,"name":"Alicia Chandler","orcid":null,"position":11,"is_corresponding":false},{"id":1482134,"name":"Evan McGilvary","orcid":null,"position":12,"is_corresponding":false},{"id":451437,"name":"Samantha G. Pattenden","orcid":"0000-0003-2057-4629","position":13,"is_corresponding":false},{"id":228877,"name":"Jian Jin","orcid":"0000-0002-2387-3862","position":14,"is_corresponding":false},{"id":593419,"name":"Daniel J. Crona","orcid":"0000-0003-3742-8863","position":15,"is_corresponding":false},{"id":266824,"name":"Nathaniel A. Hathaway","orcid":"0000-0002-9807-0167","position":16,"is_corresponding":false},{"id":536165,"name":"Travis J. Nelson","orcid":"0000-0001-7416-5885","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:40.686992Z","pmid":"41098562","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":[]}