Molecular Targets for Nutrients in Prostate Cancer Prevention . Nutritional Science Research Group Prostate and Urologic Cancer Research Group. 30. 25. 20. 15. Age-Adjusted Death Rates (per 100,000 population). 10. 5. 0. Philippines. Bulgaria. United States. Iceland. Japan.
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Prostate Cancer Prevention
Nutritional Science Research Group
Prostate and Urologic Cancer Research Group
Age-Adjusted Death Rates
(per 100,000 population)
1996 Global Prostate Cancer Mortalities
Selenium Vitamin D Vitamin E
Vitamin A Genistein
However, the Specific Mechanism is Not Defined
genetic and epigenetic research
to define molecular targets for nutrients
in prostate cancer prevention.
Effective Nutrients(Relative Effectiveness, Dose Dependency, Temporality, Consistency, Specificity)
Criteria for Molecular Targets
• Linkage to a significant proportion of prostate tumors
• Tissue specificity across various genetic backgrounds
• Modification influences tumor risk and/or behavior
Transfection Adenoviral Infection
Antisense Nucleotide Metabolic Inhibitors
Conditional Knockout Metabolic Inhibitors
Apoptosis (e.g. bcl2)
Signaling Pathways (e.g.CDKs)
Cell Senescence (e.g. Telomerase)
Tumor Suppressor Genes (e.g. pRb)
Oncogenes (e.g. c-myc)
Survival Pathways (e.g. IGF-1/PI3K/Akt)
Inflammation (e.g. NF kappa B)
Transgenic or KO Mice (PTEN, p27)
Transfection (p27, CDK2)
(Absorption and Metabolism)
• Can IGF-1, PI3K, and Akt account for the effect of dietary fatty acids on prostate tumor growth promotion?
• Can variation in AR or ER explain the ability of soy isoflavones to retard prostate cancer?
• Can GSTP1 methylation be influenced by dietary methyl donors and ultimately modify prostate cancer risk?
• National Cancer Institute Prostate Cancer Progress Review Group (1998)
• Nutrition Implementation Group (1999)
• DCP/NCI Molecular Targets for Dietary Prevention of Prostate Cancer (2000)
• National Cancer Institute’s Extraordinary Opportunities (2002)
This RFA mechanism with set-aside funds is needed to stimulate submission of innovative applications, primarily R01s.
Proposed Budget (M)(4 to 6 Awards)
0.2FY00 Extramural Portfolio Analysis
(10 R01, 2 R03,
2 U01, 1 R21)