Developmental Research Pilot Project

Anne McTiernan, MD, PhD, Fred Hutchinson Cancer Research Center

"Effect of dietary intervention on insulin and IGF-1 receptors in prostate cancer"

Abstract

Obese men at the time of diagnosis have an increased risk of prostate cancer (PCa)-specific mortality. The mechanism(s) linking obesity and PCa progression are unknown but may include hyperinsulinemia and the insulin-like growth factor (IGF) axis. In vitro and animal studies of dietary alternations have demonstrated changes in IGF-1 Receptor (IGF-R) and insulin receptor (IR) expression and PCa growth. We hypothesize that dietary modification in men with PCa decreases the expression and activation of IGF-R and IR in prostate cancer cells.

We propose to evaluate, in a randomized trial in men undergoing radical prostatectomy (RP), the changes in IGF-R and IR expression/activation in human PCa tissue after dietary intervention with the following specific aims:

• Determine the change in expression of IGF-R and IR on PCa cells in men undergoing dietary intervention compared to controls as measured by immunohistochemistry
  
• Determine changes in activation of the IGF-R and IR on PCa cells as measured by phosphorylated AKT/total AKT, and phosphorylated IGF-R/IR
  
• Determine changes in PCa proliferation as measured by Ki-67 expression

Men with low-risk PCa undergoing RP will be recruited and randomized to a 6-week nutritionist directed, caloric-restricted dietary program modified from the Diabetes Prevention Program (n=10) or given literature on a healthy diet (n=10). Tissue analyses will compare changes in receptor expression/activation between the pre-intervention prostate biopsies and the post-intervention RP specimens. These pilot data will be used to develop a larger grant application to study weight loss-dietary intervention to improve patient outcomes and reduce PCa specific mortality.

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