Colon cancer: preventive agents and the present status of chemoprevention.
BACKGROUND
Colorectal cancer (CRC) is one of the most common cancers worldwide and a prevalent cause of morbidity and mortality. CRC has a natural history of transition from a precursor lesion, ie adenomatous polyp to cancer, that spans over 10 to 15 years providing an extended opportunity for intervention and cancer prevention. Suppression of the carcinogenic process by use of pharmacological or natural agents is the cornerstone of chemoprevention.


OBJECTIVE
The aim of this review was to give an up-to-date overview on the different agents that had been studied, over the last decade, as chemopreventive agents and the current status of chemoprevention.


METHODS
Articles were identified by searches of PubMed and the Internet and reviewed. All articles and other referenced materials were retrieved using the keywords "colon cancer", "adenoma", "chemoprevention", "non steroidal anti-inflammatory drugs", "aspirin", "HMG-CoA reductase inhibitors", "bile acids", "Difluoromethylornithine", "hormone replacement therapy", "mesalamine", "curcumin", and "calcium". Papers were published between 1960 and 2008, with older references selected for historical significance. Only papers published in English were reviewed.


RESULTS
Recent preclinical as well as clinical trials have provided data on the potential benefit of a number of drugs and nutritional elements in the field of CRC prevention. Currently, only celecoxib is FDA approved for chemoprevention of CRC and only for high-risk patients with Familial Adenomatous Polyposis (FAP). This is mainly due to cardiovascular toxicity reported in individuals with a personal history of sporadic adenomas. Aspirin and sulindac have also repeatedly demonstrated efficacy in this setting. However, due to increased risk of associated GI toxicity their benefit will have to be weighed against their risk. Combination therapy, using lower doses of each medication, is drawing a great deal of attention and many studies utilizing a variety of chemopreventive agents are presently under study. Promising results have recently been published using sulindac and DFMO.


CONCLUSIONS
Many agents have shown positive results in the field of chemoprevention however, the ideal chemopreventive agent remains to be discovered with great emphasis on need not to harm. Combining different agents may maximize effectiveness while limiting drug toxicity.
Half
Elizabeth
E
Tel Aviv University, Tel Aviv Medical Center and Sackler School of Medicine, Chaim Sheba Medical Center, Tel Hashomer and Integrated Cancer Prevention Center, Department of Gastroenterology and Hepatology, Israel. betsy.half@sheba.health.gov.il
Arber
Nadir
N
D018256:Adenomatous Polyps / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D020249:Hormone Replacement Therapy; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D001647:Bile Acids and Salts; D052246:Cyclooxygenase 2 Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors