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Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors
Bandaru S Reddy1, Chinthalapally V Rao
1Nutritional Carcinogenesis and Chemoprevention Program, American Health Foundation, Valhalla, NY 10595, USA. b_reddy@ahf.org
Abstract:
During recent years, multidisciplinary studies in epidemiology and molecular biology, as well as preclinical studies, have contributed much to our understanding of the etiology of colorectal cancer; more importantly they have enabled us to approach its prevention. An impressive body of epidemiological data suggests an inverse relationship between colorectal cancer risk and regular use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. Clinical trials with NSAIDs have demonstrated that NSAID treatment caused regression of preexisting colon adenomas in patients with familial adenomatous polyposis. Preclinical efficacy studies have provided compelling evidence that several phytochemicals with antiinflammatory properties and NSAIDs act to retard, block, or reverse colon carcinogenesis. Equally exciting are opportunities for effective chemoprevention with selective cyclooxygenase-2 (COX-2) inhibitors including celecoxib and rofecoxib in a variety of preclinical models of colon cancer. Naturally occurring COX-2 inhibitors such as curcumin and certain phytosterols have been proven to be effective as chemopreventive agents against colon carcinogenesis with minimal gastrointestinal toxicity. Multistep process of carcinogenesis has provided substantial insights into the mechanisms by which naturally occurring and synthetic antiinflammatory agents modulate these events leading to suppression of tumorigenesis. Growing knowledge in this area has brought about innovative approaches using a combination of agents with different modes of action as a means of increasing efficacy and minimizing toxicity. The natural history of colorectal cancer, from dysplastic aberrant crypts to adenomas and adenocarcinomas, offers multiple opportunities for assessment and intervention. Of further importance would be to identify molecular targets that are critical in the growth and survival of the malignant colorectal cell and are modulated by NSAIDs and COX-2 inhibitors.
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) and phytochemicals show promise in preventing colorectal cancer by inhibiting inflammation and carcinogenesis. Further research into molecular targets could enhance chemoprevention strategies.
Area of Science:
- Oncology
- Molecular Biology
- Epidemiology
- Pharmacology
Background:
- Colorectal cancer (CRC) etiology is increasingly understood through multidisciplinary research.
- Epidemiological data suggest a link between reduced CRC risk and regular use of nonsteroidal anti-inflammatory drugs (NSAIDs).
- NSAIDs have shown efficacy in regressing colon adenomas in clinical settings.
Purpose of the Study:
- To explore the potential of anti-inflammatory agents, including NSAIDs and phytochemicals, in colorectal cancer prevention.
- To investigate the role of selective cyclooxygenase-2 (COX-2) inhibitors in colon cancer chemoprevention.
- To understand the mechanisms by which anti-inflammatory agents modulate colon carcinogenesis.
Main Methods:
- Review of epidemiological data and clinical trials on NSAID use and CRC risk.
- Analysis of preclinical studies on phytochemicals and synthetic COX-2 inhibitors in colon cancer models.
- Examination of the molecular mechanisms underlying the chemopreventive effects of anti-inflammatory agents.
Main Results:
- NSAIDs, including aspirin, are associated with an inverse relationship to colorectal cancer risk.
- Phytochemicals and selective COX-2 inhibitors demonstrate efficacy in preclinical models of colon cancer.
- Naturally occurring COX-2 inhibitors like curcumin show chemopreventive effects with minimal toxicity.
Conclusions:
- Anti-inflammatory agents, both synthetic and natural, offer promising avenues for colorectal cancer chemoprevention.
- Understanding the multistep process of carcinogenesis reveals targets for intervention.
- Combination therapies and identification of molecular targets are key for future strategies to increase efficacy and minimize toxicity.