{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:20:49Z","timestamp":1789737649908,"version":"4.0.1"},"reference-count":30,"publisher":"Portland Press Ltd.","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,10,30]]},"abstract":"<jats:p>Combination chemoprevention for cancer was proposed a quarter of a century ago, but has not been implemented in standard medical practice owing to limited efficacy and toxicity. Recent trials have targeted inflammation and polyamine biosynthesis, both of which are increased in carcinogenesis. Preclinical studies have demonstrated that DFMO (difluoromethylornithine), an irreversible inhibitor of ODC (ornithine decarboxylase) which is the first enzyme in polyamine biosynthesis, combined with NSAIDs (non-steroidal anti-inflammatory drugs) suppresses colorectal carcinogenesis in murine models. The preclinical rationale for combination chemoprevention with DFMO and the NSAID sulindac, was strengthened by the observation that a SNP (single nucleotide polymorphism) in the ODC promoter was prognostic for adenoma recurrence in patients with prior sporadic colon polyps and predicted reduced risk of adenoma in those patients taking aspirin. Recent results from a phase III clinical trial showed a dramatic reduction in metachronous adenoma number, size and grade. Combination chemoprevention with DFMO and sulindac was not associated with any serious toxicity. A non-significant trend in subclinical ototoxicity was detected by quantitative audiology in a subset of patients identified by a genetic marker. These preclinical, translational and clinical data provide compelling evidence for the efficacy of combination chemoprevention. DFMO and sulindac is a rational strategy for the prevention of metachronous adenomas, especially in patients with significant risk for colorectal cancer. Toxicities from this combination may be limited to subsets of patients identified by either past medical history or clinical tests.<\/jats:p>","DOI":"10.1042\/bse0460008","type":"journal-article","created":{"date-parts":[[2009,11,4]],"date-time":"2009-11-04T13:19:29Z","timestamp":1257340769000},"page":"111-124","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention"],"prefix":"10.1042","volume":"46","author":[{"given":"Nathaniel S.","family":"Rial","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724 U.S.A."},{"name":"Cancer Biology, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Frank L.","family":"Meyskens","sequence":"additional","affiliation":[{"name":"Chao Family Comprehensive Cancer Center and Departments of Medicine and Epidemiology, University of California, Irvine, CA 92868 U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene W.","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724 U.S.A."},{"name":"The University of Arizona, Department of Cell Biology and Anatomy and Gastrointestinal Cancer Program, Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2009,11,4]]},"reference":[{"key":"2021111610121556700_B1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1073\/pnas.60.4.1420","article-title":"Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors","volume":"60","author":"Russell","year":"1968","journal-title":"Proc. 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