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KMID : 0603519980030020136
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Journal of Korean Association of Cancer Prevention
1998 Volume.3 No. 2 p.136 ~ p.147
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Cancer Chemoprevention: Rationales Molecular Mechanisms, and Novel Strategies
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Chun Kyung-Soo
Surh Young-Joon
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Abstract
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Chemoprevention, which is defined as inhibition, retardation, or reversal of the process of carcinogenesis by use of relatively non-toxic chemical agents, is now considered to be one of the most promising and realistic strategies for minimizing cancer risks in humans. The rationale for cancer chemoprevention trials is based on multi-stage nature of carcinogenesis. Thus, cancer chemoprevention is the attempt to use natural and synthetic compounds to intervene in one or more of the early precancerous stages of carcinogenesis, before invasive disease begins. Chemopreventive agents are placed into two broad categories, viz, blocking agents find suppressing agents, depending on their probable sites of action in the multi-stage carcinogenesis. Blocking agents act during the initiation phase by inhibiting the formation of cancer-producing substances from precursor compounds and/or by preventing carcinogens from reacting with critical informational molecules (e.g., DNA, RNA, and proteins) in the target cells. Suppressing agents exert their protective functions at promotion and/or progression phases, thereby repressing the overall expression of neoplasia in cells previously exposed to carcinogenic agents. Some chemopreventive substances possess both blocking and suppressing activities. Successful implementation of chemopreventive strategies relies on the precise understanding of underlying molecular mechanisms. While the majority of chemopreventive supplements have been intended to halt the progression, either before or after genetic mutations cause a cell to become malignant, a new approach relies on agents that divert the progression to a benign outcome, such as the programmed death (apoptosis) or differentiation of precancerous cells, which will steer affected cells back toward their normal, noncancerous state. Suppression of prostaglandin synthesis through selective inhibition of cyclooxygenase-2 is another promising strategy applicable to identification and development of chemopreventive drugs. In this context, it is interesting to note that certain non-steroidal anti-inflammatory drugs NSAIDS), such as sulindac and piroxicam, have been shown to protect against colorectal carcinogenesis.
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KEYWORD
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Cancer chemoprevention, Chemopreventive agents, Blocking agents, Suppressing agents, Programmed cell death, Apoptosis
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