This work is based on the hypothesis that to fully exploit the benefit of cell line-based drug screening, a representative cell line panel recapitulating the varied types of prostate cancer (PCa) and the contribution of differences in ancestry is necessary. PCa is the leading cause of cancer mortality in men worldwide. Current advances in patient diagnoses and therapy have led to a decline in PCa incidence and mortality rates. However, this is not the case for men of African ancestry (MAA) from Africa and the Caribbean where both PCa incidence and mortality rates are on the rise. PCa cell lines are used to understand the biology of PCa and to advance the development of PCa theranostics. However, more than 97% of the PCa cell lines that are readily available to researchers are from men of European ancestry (MEA). There continues to be limited representation of PCa materials from MAA when compared to MEA, and there are almost no cell models available derived from MAA. This makes it difficult to assess the efficacy of potential treatments in MAA versus MEA, contributing to a problem in health disparities. To address this problem, this project will first develop and characterize cell lines that recapitulate the most prevalent molecular abnormalities associated with PCa in MAA (Aim 1). Second, it will comparatively screen chemotherapy drugs and Jamaican natural lead molecules on the novel MAA PCa cell lines to standardly employed PCa cell lines derived from MEA (Aim 2).