Abstract A27: Fidelity of a PDX-CR model for bladder cancer

Abstract

Abstract Current efforts for cancer drug discovery have predominantly been deterred by the lack of appropriate preclinical cancer models that recapitulate the characteristics of this complex disease. Patient-derived xenografts (PDXs) are widely recognized as a more physiologically relevant preclinical model than organoids and standard cell lines, and often resemble the original tumor histology, genetic profile, and gene-expression patterns. Despite these benefits, PDX models are limited by their variable engraftment rate, lack of sustained growth in vitro, low throughput for drug screening, lower amenability to experimental manipulation, and high cost. In this study, we utilized conditional reprogramming (CR) technology to generate four CR cell (CRC) lines from bladder cancer PDXs. The CR cells were then employed to evaluate the genetic status and drug sensitivity and compared with the parental PDX tumors. All the established CRC lines maintained parental mutations and allele frequencies without clonal drift. Moreover, the drug responses of the parental PDX tumors in vivo were retained in the established CRC lines in vitro. Altogether, CR technology offers the ability to generate cell lines and expand PDX cells without compromising fundamental biologic properties of the model, thereby allowing for in vitro use to reduce animal usage, variability, and study cost. Perhaps more importantly, the CR cell lines established here can be used for personalized high-throughput drug screening as well as for studying drug-resistance mechanisms. Citation Format: Abdul M. Mondal, Ai-Hong Ma, Guangzhao Li, Ewa Krawczyk, Lu Jie, Richard Schlegel, Chong-Xian Pan, Xuefeng Liu. Fidelity of a PDX-CR model for bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A27.