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Citation
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HERO ID
6746768
Reference Type
Journal Article
Subtype
Review
Title
Cancer chemoprevention drug targets
Author(s)
Krishnan, K; Campbell, S; Abdel-Rahman, F; Whaley, S; Stone, WL
Year
2003
Is Peer Reviewed?
Yes
Journal
Current Drug Targets
ISSN:
1389-4501
Volume
4
Issue
1
Page Numbers
45-54
Language
English
PMID
12528989
DOI
10.2174/1389450033347028
Web of Science Id
WOS:000180173500005
Abstract
Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Chemoprevention can either prevent DNA damage that initiates the neoplastic transformation process or reverses the progression of pre-invasive lesions. Epidemiological observations, experimental evidence from animal carcinogenesis models, knock-out models, cancer cell lines and clinical trials have shown the efficacy of this approach. Recent advances in our understanding of carcinogenesis have led to the synthesis of new drugs that target specific receptors. Non-steroidal anti-inflammatory drugs target the prostaglandin pathway. The identification of the role of cyclooxygenase-2 in epithelial carcinogenesis led to the synthesis of selective cyclooxygenase-2 inhibitors (Celecoxib). Celecoxib was subsequently approved for the prevention of colon polyps in familial adenomatous polyposis after the completion of a randomized clinical trial. The large chemoprevention clinical trial with the selective estrogen receptor modulator, tamoxifen, showed the benefit of tamoxifen in the prevention of breast cancer in high-risk women. Retinoids and rexinoids target the retinoid receptors and have a role in chemoprevention of aerodigestive, hepatic and cervical neoplasia. Selenium, an inhibitor of the glutathione peroxidase system, is being tested in the chemoprevention of prostate cancer and lung cancer. The different isoforms of vitamin E (tocopherols) may be chemopreventive. Recent evidence indicates that gamma-tocopherol may be a more powerful chemopreventive than the alpha-tocopherol. The review details the rationale, experimental and clinical evidence and the drug targets of the chemopreventive agents that are currently in various phases of clinical development.
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