Abstract 1717: Establishment and characterization of enzalutamide resistant prostate CDX models

Abstract Prostate cancer (PCa) is common and mostly androgen dependent cancer occurred in men and ranked fifth of the causes of death over the world, reduction the serum level of androgen become the priority therapy method for treating PCa patients. Although the first generation of anti-androgen receptor (AR) new drugs such as flutamide, nilutamide, and bicalutamide were launched few years ago and lighted new hopes for treatment of androgen dependent PCa, drug resistance was developed quickly and push the second generation of anti-AR drugs such as enzalutamide, apalutamide, and darolutamide to the market by their high specific binding to AR and better drug efficacy. Despite new anti-AR drugs exerted better efficacy, drug resistance still hampered the treatment of PCa patients, new challenge was burst for anti-PCa drugs through AR pathway. In this study, we developed an enzalutamide resistant C4-2B cell line in vitro by escalated the enzalutamide concentration gradually. The phenotype and genotype of C4-2B cell line were checked while enzalutamide concentration was increased. After 6 months of induction and identification, C4-2B enzalutamide resistant cell line was established and showed 140 times of drug-resistant index compare to that of parental cell. The in vivo drug-resistant efficacy was also confirmed in C4-2B enzalutamide resistant (C4-2B Enz-R) CDX models using 30 mpk enzalutamide through PO administration for 28 days (TGI=8.37%, T/C=93.22%) compared to the enzalutamide efficacies on LNCAP and 22RV1 CDX models. Western blot for androgen receptor expression level in tumor tissues and ELISA assay for prostate specific androgen (PSA) level in serum are highly correlated to the tumor volume of C4-2B Enz-R CDX models. The well characterized novel C4-2B Enz-R cell line and CDX model were appropriate for new drug discovery of anti-PCa drugs through AR pathway in vitro and in vivo. Citation Format: Haiting Dai, Jie Yang, Xiu Fan, Wen-Jen Yu. Establishment and characterization of enzalutamide resistant prostate CDX models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1717.