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DFMO: targeted risk reduction therapy for colorectal neoplasia.

Abstract
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.
AuthorsChristina M Laukaitis, Eugene W Gerner
JournalBest practice & research. Clinical gastroenterology (Best Pract Res Clin Gastroenterol) Vol. 25 Issue 4-5 Pg. 495-506 (Aug 2011) ISSN: 1532-1916 [Electronic] Netherlands
PMID22122766 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Anticarcinogenic Agents
  • Enzyme Inhibitors
  • Ornithine Decarboxylase Inhibitors
  • Ornithine Decarboxylase
  • Eflornithine
Topics
  • Adenoma (enzymology, pathology, prevention & control)
  • Animals
  • Anticarcinogenic Agents (therapeutic use)
  • Chemoprevention
  • Colorectal Neoplasms (enzymology, pathology, prevention & control)
  • Eflornithine (therapeutic use)
  • Enzyme Inhibitors (therapeutic use)
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Recurrence, Local (prevention & control)
  • Ornithine Decarboxylase (metabolism)
  • Ornithine Decarboxylase Inhibitors
  • Precancerous Conditions (drug therapy, enzymology, pathology)
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

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