{"doi":"10.3390/ijms262110808","title":"STAT3 Inhibition to Treat Ulcerative Colitis-Associated Colorectal Cancer","abstract":"In patients with inflammatory bowel disease (IBD), colorectal cancer (CRC) occurs with 20-to-30-fold higher frequency, is more advanced at diagnosis, and has a worse prognosis than in the general population. To improve their treatment options, we determined if targeting STAT3 with TTI-101, a small-molecule STAT3 inhibitor, was beneficial in the azoxymethane (AOM)-disodium sulfate (DSS) mouse model of colitis-associated CRC. C57BL/6 mice received a single intraperitoneal injection of AOM followed by three cycles of 5% DSS in drinking water before receiving TTI-101 (50 mg/kg by oral gavage, OG, and daily) or vehicle for 28 days. TTI-101 treatment reduced adenoma numbers by 89% from 1.14 ± 1.07 in vehicle-treated mice to 0.13 ± 0.35 in TTI-101-treated mice (p ≤ 0.05, Kruskal–Wallis test). Levels of activated STAT3 (pY-STAT3) were increased 3.3-fold in the epithelium and stroma of dysplastic mucosa (147 ± 46; mean ± SD; and n = 4) vs. normal mucosa (45 ± 26; n = 7; and p ≤ 0.05, Kruskal–Wallis test) and were correlated with the adenoma number. TTI-101 was detected at pharmacologically relevant levels in the plasma and colons of TTI-101-treated AOM-DSS mice and was concentrated within colon tissue; plasma TTI-101 levels inversely correlated to pY-STAT3 levels. Importantly, TTI-101 normalized the colon transcriptome of AOM-DSS mice and reduced the expression of STAT3- and STAT1-upregulated genes associated with CRC oncogenesis. Thus, TTI-101 treatment may benefit IBD patients with CRC.","journal":"International Journal of Molecular Sciences","year":2025,"id":535317,"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":2,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"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":1418911,"name":"Zal Italia","orcid":"0009-0001-3174-5406","position":1,"is_corresponding":false},{"id":1418912,"name":"Zara Italia","orcid":"0009-0001-3086-741X","position":2,"is_corresponding":false},{"id":1418913,"name":"Tan Hoang","orcid":"0009-0008-4033-8862","position":3,"is_corresponding":false},{"id":848064,"name":"Emma Rodrı́guez","orcid":"0000-0002-5509-5321","position":4,"is_corresponding":false},{"id":717254,"name":"T. Kris Eckols","orcid":null,"position":5,"is_corresponding":false},{"id":238597,"name":"Moses M. Kasembeli","orcid":null,"position":6,"is_corresponding":false},{"id":1365299,"name":"Leticia Hamana","orcid":"0000-0001-5952-320X","position":7,"is_corresponding":false},{"id":228168,"name":"Luisa M. Solis Soto","orcid":"0000-0002-1253-630X","position":8,"is_corresponding":false},{"id":252485,"name":"Rajasekaran Mahalingam","orcid":"0000-0003-2228-5628","position":9,"is_corresponding":false},{"id":235092,"name":"David J. Tweardy","orcid":"0000-0001-8492-8460","position":10,"is_corresponding":false},{"id":235091,"name":"Prema Robinson","orcid":"0000-0002-6798-4839","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41226842","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":[]}