Abstract B004: Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2

Abstract

Abstract Prostate cancer incidence and mortality rates are remarkably higher in African-American (AA) men as compared to their European-American (EA) counterparts even after factoring in socio economic status. The disproportionate incidence of prostate cancer and associated mortality in African men is currently becoming more evident as Several studies have reported significant variations in genetic, molecular, epigenetic, microRNA, and cell signaling pathways in patients of Caucasian and African race. As androgen is implicated in prostate cancer progression and about 90% of the cases are Androgen-dependent, blocking androgen action is an effective strategy in treating prostate cancer. Previously, we reported that galeterone and VNPP433-3β, a next generation galeterone analog potently inhibit metastatic castration resistant prostate cancer of Caucasian origin in vitro and in vivo by degrading AR/AR-V7 and Mnk1/2. Since the prostate cancer patients of African descent express significant levels of AR and Mnk1/2, we investigated the efficacy of galeterone and VNPP433-3β in treating prostate cancer of African men. Cell proliferation assay using the cell lines MDA-PCa 2b and RC77 T/E derived from AA prostate cancer patient demonstrates that galeterone and VNPP433-3β can effectively inhibit prostate cancer of African descent at very low concentration. These cell lines are Androgen-sensitive and further biochemical studies reveal that galeterone and VNPP433-3β degrade AR and Mnk1/2 in RC77 T/E and MDA-PCa 2b cell lines, thereby inhibiting its proliferation. Galeterone and VNPP433-3β significantly decrease the half-life of AR in these cell lines by increasing the rate of ubiquitination and proteasomal degradation of AR. Therefore, galeterone and VNPP433-3β hold significant promise for the clinical management of prostate cancer in patients of African descent Citation Format: Elizabeth Thomas, Retheesh Sulochana Thankan, Puranik Purushottachar, Vincent C.O. Njar. Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2 [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B004.