Our overall objective in the current application is to establish the viability of a new strategy of treating late stage PCa through therapeutic targeting of cholesterol metabolism in vivo, using combination of cutting edge spectroscopic imaging and other technologies, including biochemistry assays and preclinical testing. The innovation of this study is that it targets altered cholesterol metabolism, an understudied field of cancer research. Our central hypothesis is that abrogating cholesterol esterification events will result in an effective strategy for treating late stage PCa. This hypothesis will be tested by first validating the presence of altered cholesterol metabolism in human prostate cancer patient specimens. We will then evaluate the therapeutic benefit of CE depletion in appropriate animal models of PCa, and elucidate pathways linking cholesterol metabolism with cancer aggressiveness. An interdisciplinary research team has been assembled, with expertise in spectroscopic imaging and nanomedicine Dr. J. X. Cheng, PI, biochemistry Dr. X. Liu, co-PI, and prostate cancer biology Dr. T. Ratliff, co-PI.