Grants - Virginia - Designated Grants - 2019

James Larner, M.D. & David Brautigan, Ph.D.

Funded by the V Foundation’s Virginia Vine event

Prostate cancer afflicts one in seven men and is their second leading cause of death, justifying development of more effective therapies. Prostate cancer depends on testosterone binding to and activating the androgen receptor (AR), which in turn promotes the growth of prostate cancer. Current therapies for prostate cancer are aimed at reducing AR activity, either by blocking the production of testosterone or through agents which compete with testosterone for binding to the AR. Our approach is depleting cancer cells of the AR protein by promoting its degradation. We will accomplish this by manipulating the pathways (either genetically or with drugs) which control protein degradation. Our preliminary data show that we can promote degradation of the AR in cells in test tubes. In this proposal we will test if we can promote AR degradation in mouse models of prostate cancer.