NDLI: Targeting Drug-Metabolizing Enzymes for Effective Chemoprevention and Chemotherapy

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Targeting Drug-Metabolizing Enzymes for Effective Chemoprevention and Chemotherapy

Content Provider	PubMed Central
Author	Swanson, Hollie I. Njar, Vincent C. O. Yu, Zhen Castro, David J. Gonzalez, Frank J. Williams, David E. Huang, Ying Kong, Ah-ng T. Doloff, Joshua C. Ma, Jie Waxman, David J. Scott, Emily E.
Abstract	The primary focus of chemoprevention research is the prevention of cancer using pharmacological, biological, and nutritional interventions. Chemotherapeutic approaches that have been used successfully for both the prevention and treatment of a number of human malignancies have arisen from the identification of specific agents and appropriate molecular targets. Although drug-metabolizing enzymes have historically been targeted in attempts to block the initial, genotoxic events associated with the carcinogenic process, emerging evidence supports the idea that manipulating drug-metabolizing enzymes may also be an effective strategy to be used for treating tumor progression, invasion, and, perhaps, metastasis. This report summarizes a symposium that presents some recent progress in this area. One area of emphasis is the development of a CYP17 inhibitor for treatment of prostate cancer that may also have androgen-independent anticancer activity at higher concentrations. A second focus is the use of a mouse model to investigate the effects of aryl hydrocarbon receptor and Cyp1b1 status and chemopreventative agents on transplacental cancer. A third area of focus is the phytochemical manipulation of not only cytochrome P450 (P450) enzymes but also phase II inflammatory and antioxidant enzymes via the nuclear factor-erythroid 2-related factor 2 pathway to block tumor progression. A final highlight is the use of prodrugs activated by P450 enzymes to halt tumor growth and considerations of dosing schedule and targeted delivery of the P450 transgene to tumor tissue. In addition to highlighting recent successes in these areas, limitations and areas that should be targeted for further investigation are discussed.
Related Links	http://dx.doi.org/10.1124/dmd.109.031351
Ending Page	544
Page Count	6
Starting Page	539
File Format	PDF
ISSN	00909556
e-ISSN	1521009X
Journal	Drug Metabolism and Disposition
Issue Number	4
Volume Number	38
Language	English
Publisher	The American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2010-04-01
Access Restriction	Open
Rights Holder	The American Society for Pharmacology and Experimental Therapeutics
Subject Keyword	Pharmacology Pharmaceutical Science Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmaceutical Science

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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