Chemoprevention of colorectal cancer - a new target needed?
OBJECTIVE
Novel treatments for colorectal cancer (CRC) include chemoprevention. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first to be studied and an inverse association was proven between their use and the development of invasive CRC. The numerous side effects of NSAIDs led, however, to the search for safer drugs. These have included Coxibs (selective COX-2 inhibitors). In this study, the role of coxibs in the chemoprevention of CRC is reviewed.


RESULTS
Numerous in-vitro and in-vivo experiments have shown the effectiveness of coxibs in the chemoprevention of CRC. These have led to the registration of celecoxib by the USA Food and Drug Administration for the treatment of familial adenomatous polyposis. Further studies of coxibs have revealed an increased risk of serious cardiovascular events when compared with placebo. This finding has considerably decreased the opportunities for chemoprevention of CRC.


CONCLUSIONS
The multi-directional activity of coxibs, which was the reason for their effectiveness against CRC development may be the key to proposing a new target area for chemoprevention. It has been shown that celecoxib partly inhibits the activity of NF-kappaB, transcription factor involved in inflammation and carcinogenesis pathways. Modulation of its activation may be the future of effective CRC chemoprevention.
Spychalski
M
M
Department of General and Colorectal Surgery, Medical University of Lodz, Lodz, Poland. nik@toya.net.pl
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D011125:Adenomatous Polyposis Coli / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic
D052246:Cyclooxygenase 2 Inhibitors; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human