{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:40:10Z","timestamp":1790361610881,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1P50CA221707\u201401A1"],"award-info":[{"award-number":["1P50CA221707\u201401A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b1 1.07 in vehicle-treated mice to 0.13 \u00b1 0.35 in TTI-101-treated mice (p \u2264 0.05, Kruskal\u2013Wallis test). Levels of activated STAT3 (pY-STAT3) were increased 3.3-fold in the epithelium and stroma of dysplastic mucosa (147 \u00b1 46; mean \u00b1 SD; and n = 4) vs. normal mucosa (45 \u00b1 26; n = 7; and p \u2264 0.05, Kruskal\u2013Wallis 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.<\/jats:p>","DOI":"10.3390\/ijms262110808","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"10808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["STAT3 Inhibition to Treat Ulcerative Colitis-Associated Colorectal Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Prema","family":"Robinson","sequence":"first","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3174-5406","authenticated-orcid":false,"given":"Zal","family":"Italia","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3086-741X","authenticated-orcid":false,"given":"Zara","family":"Italia","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4033-8862","authenticated-orcid":false,"given":"Tan","family":"Hoang","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Kris","family":"Eckols","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses","family":"Kasembeli","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5952-320X","authenticated-orcid":false,"given":"Leticia Hamana","family":"Zorrilla","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-630X","authenticated-orcid":false,"given":"Luisa Maren Solis","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasekaran","family":"Mahalingam","sequence":"additional","affiliation":[{"name":"Department of Symptom Research Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8492-8460","authenticated-orcid":false,"given":"David J.","family":"Tweardy","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"},{"name":"Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2023). 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