Abstract 1214: Preclinical models of prostate cancer: New patient-derived xenografts for preclinical studies and evaluation of prostate cancer biology

Abstract

Abstract Prostate cancer (PCa) is a heterogeneous disease and in order to increase our understanding of PCa biology and evaluate efficacy of novel pipeline agents, clinically relevant models are needed. It is well known that PCa xenografts are difficult to establish and propagate with approximate take rates of only 20%. During past the 20 years we have established and characterized a large series of LuCaP prostate cancer patient-derived xenografts (PDXs). Herein, we present a summary of the biological and molecular characterization of these PDX LuCaP models. LuCaP PCa PDX models were derived from primary PCa and various sites of metastases. The histology of the LuCaP PDXs is similar to the originating clinical specimen, and the unsupervised gene expression array clustering analyses revealed an association between the xenograft and the originating specimen. Twenty four of the lines are adenocarcinoma and four exhibit a neuroendocrine phenotype. Characterization of the LuCaP PDX tumors includes expression arrays, RNASeq, exome sequencing, and IHC for multiple markers. Some of the models show Rb deletion, TMPRSS2/ERG translocation, PTEN deletion, PI3K activation and other critical characteristics detected in clinical specimens and associated with PCa progression. In vivo characterizations show responses to androgen suppression spanning the range of responses to this therapy seen in patients; differential levels of serum PSA, tumor-doubling time, and responses to docetaxel. Furthermore, seven of our models elicit an osteoblastic reaction when implanted in the bone. In summary the diversity of phenotypes and responses of the LuCaP PDXs to therapy are representative of responses seen in the clinical setting. Therefore, the LuCaP PCa PDXs are highly clinically relevant models to study PCa biology and evaluate new treatment modalities. These models are available to researchers worldwide for studies aiming to improve survival of PCa patients and quality of life of men suffering from this disease. Citation Format: Holly M. Nguyen, Colm Morrissey, Peter S. Nelson, Xiaotun Zhang, Paul H. Lange, Robert L. Vessella, Eva Corey. Preclinical models of prostate cancer: New patient-derived xenografts for preclinical studies and evaluation of prostate cancer biology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1214. doi:10.1158/1538-7445.AM2014-1214