Chemoprevention Strategies

Dunlap, T. Chandrasena, R. E. P. Wang, Z. Sinha, V. Wang, Z. Thatcher, G. R. J. Quinone formation as a chemoprevention strategy for hybrid chugs balancing cytotoxity and cytoprotection. Chem. Res. Toxicol. 2007, 20, 1903-1912. 

Colorectal Cancer Chemoprevention Strategies Targeting Bile Acids (Illustrated in Figure 5.2)... 

Figure 5.2 Therapeutic interventions for decreasing colorectal mucosal bile acid exposure as a CRC chemoprevention strategy. 1) Lifestyle modifications including reduction in dietary animal fat and increased fibre intake may, at least partly, be explained by reduction in luminal primary (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary (deoxycholic acid [DCA] and lithocholic acid [LCA]) bile acids. 2) Reduction of secondary bile acids, which are believed to have pro-carcinogenic activity could be obtained by decreased bacterial conversion from primary bile acids. 3) Alternatively, bile acids could be sequestered by chemical binding agents, e.g. aluminium hydroxide (Al(OH)3) or probiotic bacteria. 4) Exogenous ursodeoxycholic acid (UDCA) can reduce the luminal proportion of secondary bile acids and also has direct anti-neoplastic activity on colonocytes in vitro.

Pathak, S.K. et al., Oxidative stress and cyclooxygenase activity in prostate carcinogenesis, targets for chemopreventive strategies, Eur. J. Cancer, 41(1), 61, 2005. 

Lynch snggests that CRC is an excellent model for investigating cancer prevention throngh means of secondary approaches snch as polypectomy for removal of precursor colonic adenomas as well as primary (chemoprevention) strategies. Attention was appropriately called to the manner in which the regular use of aspirin and other NSAIDs has led to a reduction in risk of CRC. Herein, a possible mechanism from this beneflt relates to the mentioned decreased prostaglandin production,... 

This study is based upon general-population expectations of CRC risk. The use of aspirin may prove more cost effective than colonoscopy when considering patients at inordinately high genetic risk for CRC, such as those patients from HNPCC famihes. Furthermore, since common polymorphisms in drag-metabolizing systems may affect the efficacy of aspirin in colorectal neoplasia prevention," it is possible that these factors can be used to individualize chemopreventive strategies. 

THE RATIONALE FOR USING DIETARY CHEMOPREVENTIVE STRATEGIES TO INHIBIT ANGIOGENESIS... 

Despite the lack of in vivo data, there is a substantial body of in vitro data published on the topic of dietary antioxidant compounds and their antiangiogenic capabilities. This provides the scientific foundation to justify pursuing dietary chemoprevention strategies to irrhibit angiogenesis in an in vivo setting. Anthocyarrins are flavonoid glycosides formd in berries with antioxidant properties." The ability of endothelial cells to incorporate... 

Dietary chemopreventive strategies aimed at inhibiting angiogenesis are an alluring option to treat a variety of neoplasms. While it is unlikely that one approach will fit all cancers, it is imperative to develop models that permit experimental manipulation to identify optimal formulations of these naturally occurring compounds. As in vivo models become more standardized, the rate of data accumulation and the ability to define how dietary compounds affect signal transduction, gene expression, and cell behavior will be enhanced. Endothelial cell neoplasms are well suited for these purposes and should be utilized to collect in vivo data to increase the likelihood of success once clinical trials with human subjects are initiated. 

Boone, C.W., Kelloff, G. J., and Steele, V.E., Natural history of intraepithehal neoplasia in humans with imphcations for cancer chemoprevention strategy. Cancer Res., 52,1651-1659,1992. 

Liberman, R., Prostate cancer chemoprevention strategies for designing efficient clinical trials. Urology, 57, 224-229, 2001. 

Tan XL, Spivack SD (2009) Dietary chemoprevention strategies for induction of phase II xenobiotic-metabolizing enzymes in lung carcinogenesis a review. Lung Cancer 65 129-137... 

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