Abstract IA20: Challenges, opportunities, and lessons learned in the bench-to-bedside translation of xenopatient studies

Abstract

Abstract Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. This is thought to be largely due to the inability of cell culture and cell line xenograft models to faithfully recapitulate the complex genetic and histologic heterogeneity of tumors. Patient-derived xenograft (PDX) models, the topic of this meeting, have been shown to be biologically stable when passaged in mice in terms of global gene expression patterns, mutational status, drug responsiveness, and tumor architecture, thus providing an opportunity for more efficient and effective preclinical drug development. Potential applications include initial drug activity screening, biomarker development, assessment of combination strategies, and more recently, testing of immunotherapy strategies in humanized PDX models. With escalating concerns over heterogeneity between primary and metastatic sites and within the tumor itself, PDX models may also provide a platform for studying the evolution of heterogeneity, particularly within the context of drug resistance mechanisms. Despite all of the theoretical advantages of these models and potential novel applications, academic labs, which operate on a smaller scale than industry, must continue to refine and assess the opportunities and limitations of PDX models in order to ensure the greatest bench-to-bedside translation of novel therapies. Our group has been working with PDX models over the last seven years and has developed a large and robust bank of PDX models of which the majority has undergone full genomic annotation. In this session on practical applications of PDX models, specific examples will be presented that represent distinct scenarios of preclinical development within the context of the opportunities, challenges, and lessons learned in utilizing these models in xenopatient trials. There is no doubt that PDX models represent a more clinically relevant platform for oncology drug development, but it will be important to recognize their strengths and weaknesses in order to fully exploit their potential in the drug development process. This is particularly important for academic labs where partnerships with industry are valuable and resources may be limited. Citation Format: S. Gail Eckhardt, Todd Pitts, Aik Choon Tan, Stacey Bagby, John Arcaroli, Anna Capasso, Kit Wong, Peter Klauck, Wells Messersmith, S Lindsey Davis, Christopher Lieu, Stephen Leong, Jennifer Diamond, John Tentler. Challenges, opportunities, and lessons learned in the bench-to-bedside translation of xenopatient studies. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA20.