Abstract C054: Current anticancer drugs differentially impact Black and White prostate cancer cell lines

Abstract

Abstract Introduction/Background: In pre-clinical models of prostate cancer (PCa) such as the utilization of cell lines, it is important to address the limited diversity present. This acknowledgment is vital to facilitate equitable assessment of the efficacy and safety of drug development across various races and ethnicities. Of all commercially available PCa cell lines, 98% of them are of European origin. The genetic and biological disparities between PCa cell lines derived from men of European ancestry (MEA) and men of African ancestry (MAA) may underlie the observed enhanced responsiveness of tumours to existing anticancer agents in MEA compared to MAA. This difference is notable given that MAA are 2.5 times more likely to succumb to PCa. This study compared the cytotoxic effects of five anticancer drugs (Docetaxel, Cabazitaxel, Abiraterone, Olaparib, Enzalutamide) and the natural product betaine on MAA (ACRJ-PC28, MDA-PCA-2b) and MEA (DU-145, PC-3) PCa cell lines. Method: After a 72-hour treatment with the anti-cancer drugs and the natural product, the inhibitory effects of these anti-cancer agents on the four cell lines were investigated using three different assays. CellTiter Aqueous, Neutral Red, and Crystal Violet assays were utilized due to distinct growth patterns observed in the various cell lines. By comparing the optical density (OD) readings and examining the cellular morphology through microscopic visualization, we aimed to determine which assay(s) yielded the most reliable results in determining accurate IC50 values. Results: Drug selectivity was observed for Abiraterone and Olaparib that were most effective in ACRJ-PC28 (IC50 = 1.10 μM) and PC-3 (IC50 = 0.28 μM) cells compared to the other PCa cell lines. Enzalutamide differentially impacted MAA, (IC50= 206 μM for ACRJ-PC28 and 104 μM for MDA-PCA-2b) and MEA (IC50 = 37 μM for PC-3 and 48 μM for DU-145) PCa cell lines. However, no distinct impact was observed for Docetaxel (IC50s = 0.05 nM for ACRJ-PC28; 0.08 nM for MDA-PCA-2b, 0.07 nM for PC-3 and 0.08 nM for DU-145) and Cabazitaxel ((IC50s = 0.56 nM for ACRJ-PC28; 0.45 nM for MDA-PCA-2b, 0.43 nM for PC-3 and 0.38 nM for DU-145) as both drugs impacted the cell lines very potently in the nM range. Conclusion: Due to the heterogenous nature of cancers, especially in PCa, a single drug or drug class may not be the best course of treatment. Instead, a combination of drugs with different mechanisms may be more suitable for addressing the diversity in cancer types. This points to the evolving understanding of personalized cancer treatment, where a strategic integration of first, second, and third-line therapies can effectively address the genetic and epigenetic factors that are unique to individuals in cancer management. Citation Format: Simone Badal, Bor-Jang Hwang, Ashlianne Nelson, Kristoff Frank, Rory Thompson, Belinda Morison, Valerie Marah, Camille Ragin. Current anticancer drugs differentially impact Black and White prostate cancer cell lines [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C054.