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Mechanisms of Chemoprevention*

Zbigniew Walaszek, PhD; Margaret Hanausek, PhD; Thomas J. Slaga, PhD
Author and Funding Information

*From the AMC Cancer Research Center, Denver, CO.

Correspondence to: Thomas J. Slaga, PhD, AMC Cancer Research Center, 1600 Pierce St, Denver, CO 80214; e-mail: slagat@amc.org



Chest. 2004;125(5_suppl):128S-133S. doi:10.1378/chest.125.5_suppl.128S-a
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The induction of cancer (carcinogenesis) depends on inherited and acquired susceptibility factors, on exposure to initiation factors (exogenous and endogenous carcinogens), and on promotion and progression factors. Chemoprevention, namely inhibition or reversal of carcinogenesis, may be conducted at variety of time points in this process to reduce occurrence of in situ or invasive cancers (primary intervention at earlier stages in the process) or cancer morbidity and/or mortality (secondary intervention at later stages in the process). As broadly defined above, chemoprevention applies to the prevention of clinical cancer by the administration of pharmaceuticals or dietary constituents. The efficacy of such prevention interventions is evaluated in clinical trials. Phase I trials determine the dose-related safety of drugs and frequently include pharmacokinetic studies. Phase II and III trials are used to test drug activity. Agents used in successful phase II clinical trials have evidence of chemopreventive efficacy and the high likelihood of the agent preventing cancer at the target site. They must have a high margin of safety and a logical presumed mechanism of chemopreventive activity. The availability of effective chemoprevention agents is only one component of a full chemoprevention program. Another important component is the availability of a marker or markers, which can help evaluate the effects of chemopreventive agents early during the prevention trials and evaluate individuals as to the magnitude of general or site-specific risk to cancer. Many of the molecular markers, such as activating mutations in oncogenes and inactivating mutations in tumor suppressor genes, can often be detected in earlier stages of cancer development. The development of new cancer preventive agents and the evaluation of efficacy of novel biological or molecular markers as intermediate end points in prevention trials are important avenues in cancer research.

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