DFMO: Targeted risk reduction therapy for colorectal neoplasia

被引：40

作者：

Laukaitis, Christina M. ^{[1
]}

Gerner, Eugene W. ^{[2
]}

机构：

[1] Univ Arizona, Dept Med, Tucson, AZ 85724 USA

[2] Univ Arizona, Dept Cellular & Mol Med, Oro Valley BIO5, Tucson, AZ 85737 USA

来源：

BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY | 2011年 / 25卷 / 4-5期

基金：

美国国家卫生研究院;

关键词：

DFMO; Chemoprevention; colorectal cancer; Polyamines; FAMILIAL ADENOMATOUS POLYPOSIS; ORNITHINE-DECARBOXYLASE GENE; ALPHA-DIFLUOROMETHYLORNITHINE OTOTOXICITY; ACTIVATED IRREVERSIBLE INHIBITOR; INDUCED POLYAMINE DEPLETION; HCL 13.9-PERCENT CREAM; BREAST-CANCER CELLS; DOUBLE-BLIND TRIAL; COLON-CANCER; PHASE-II;

D O I：

10.1016/j.bpg.2011.09.007

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Strategies to decrease intracellular polyamine levels have been studied for their efficacy in reducing colorectal cancer (CRC) risk. A successful strategy combined agents that decreased polyamine synthesis by inhibiting ornithine decarboxylase with difluoromethylornithine (DFMO), and increased cellular export of polyamines by activating the spermidine/spermine acetyl transferase with non-steroidal anti-inflammatory drugs (NSAIDs). A Phase III trial treating resected adenoma patients with DFMO plus sulindac demonstrated marked reduction of metachronous adenomas, advanced adenomas and multiple adenomas compared to placebo. This combination regimen was well-tolerated, however there was a non-significant excess of cardiovascular events in the treatment arm compared to placebo as well as modest ototoxicity. Targeting this therapy to people at elevated risk of CRC, and employing clinical and genetic predictors, should improve patient benefit and reduce the risk of side effects to improve the acceptability of this strategy. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：495 / 506

页数：12

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