Abstract 43: Establishment and characterization of prostate adenocarcinoma XPDX models from naïve and pretreated patients

Abstract Background: Preclinical models of prostate adenocarcinoma (PAC) are challenging to develop and maintain. We previously reported (AACR2022/ENA2023) the successful establishment and characterization of four parental and three conditioned prostate adenocarcinoma models in intact immunodeficient male mice. Using this experience, we have expanded our platform with six additional PAC models designated ST6084, ST6838, ST7482, ST7695, STF1159 and STM344. These models were characterized for receptor expression, genomic alterations, and in vivo drug sensitivity to relevant therapies. Methods: XPDX models representing prostate cancer were established from primary (ST6084, ST6838, ST7695, STF1159) or metastatic (ST7482, STM344) samples implanted into intact CB-17 SCID mice. Resulting models were passaged serially and further developed in both intact and castrated mice until growth stabilization. Resulting models were characterized using genomic analysis, including WES and RNAseq, receptor expression, and in vivo drug sensitivity studies. For in vivo studies, docetaxel, abiraterone and enzalutamide were evaluated at standard treatment regimens. Study endpoints included tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion; a %T/C of ≤ 20% versus control was considered sensitive. Tumor regression (%T/C<0%) versus Day 0 tumor volume was also reported. Results: Most models lacked AR or PSMA staining but ST6838 and STM344 were positive for AR-V7. Genomic characterization identified KDM6A loss in ST7482, a model from a patient post-apalutamide. An ATM aberration was present in both ST7482 and STM344, the latter derived from a patient post-chemo and targeted therapies including a five-month response on an ATR inhibitor. No tested models were sensitive to abiraterone or enzalutamide (%T/C>20%) and only ST7482 was sensitive to docetaxel. Conclusion: We have established and characterized an expanded panel of PAC XPDX models. These models can be utilized as a valuable tool in better understanding prostate cancer and in developing novel therapies for drug-resistant patients. Citation Format: Johnnie Flores, Alyssa Simonson, Anna Stackpole, Jennifer Garcia, Shaquille Johnson, Pedro Cesenes, Mia Lopez, Peter Forofontov, Lisa Gonzales, Garrett Mercer, Amarissa Rojas, Nehal Lakhani, Emiliano Calvo, Andrew Cunningham, Michael J. Wick. Establishment and characterization of prostate adenocarcinoma XPDX models from naïve and pretreated patients. [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 43.