{"doi":"10.3390/cancers17132087","title":"Tropisetron Suppresses Chronic Pancreatitis and Pancreatic Cancer by Blocking Interleukin 33 Expression","abstract":"Background/Objectives: Chronic inflammation is a key driver of cancer. Interleukin 33 (IL-33) has emerged as a crucial factor involved in the pathogenesis of cancer-prone chronic inflammation. IL-33 functions as a cytokine and a nuclear protein to initiate chronic inflammation and cancer. However, small molecules capable of suppressing IL-33 expression to block its cytokine and nuclear functions are underexplored. Methods: The impact of tropisetron on IL-33 expression and its role in suppressing pancreatitis and pancreatitis-mediated pancreatic cancer were examined. Results: We demonstrate that tropisetron suppresses IL-33 expression, with high potential to serve as a novel therapeutic strategy for preventing chronic inflammation and its cancer sequela. Through screening 1018 Food and Drug Administration (FDA)-approved drugs, we discovered that tropisetron, a 5-hydroxytryptamine type 3 (5-HT3) antagonist commonly used to prevent and treat nausea and vomiting, effectively blocked IL-33 expression by suppressing IRF3 activation. Tropisetron inhibited pancreatitis and its progression to pancreatic cancer in mice. Conclusions: Tropisetron is an IL-33 inhibitor and can provide a novel therapeutic strategy to prevent and treat chronic pancreatitis and its associated cancer.","journal":"Cancers","year":2025,"id":544926,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":1136175,"name":"Mahsa Mortaja","orcid":null,"position":1,"is_corresponding":false},{"id":1270610,"name":"YeePui Yeung","orcid":null,"position":2,"is_corresponding":false},{"id":858093,"name":"Jiao Huang","orcid":"0000-0002-6275-0451","position":3,"is_corresponding":false},{"id":653527,"name":"Jong Ho Park","orcid":"0000-0002-0488-7791","position":4,"is_corresponding":false},{"id":441396,"name":"Shadmehr Demehri","orcid":"0000-0002-7913-2641","position":5,"is_corresponding":false},{"id":1370337,"name":"An-Na Bae","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:17.418915Z","pmid":"40647388","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":[]}