AACR 2015: A patient-centric repository of PDX models for translational oncology research
A patient-centric repository of PDX models for translational oncology research
Tin Khor1, Ido Ben-Zvi1, Amanda Katz1, David Vasquez-Dunddel1, Ido Sloma1, Daniel Ciznadija1, David Sidransky2, Keren Paz1. 1Champions Oncology, Baltimore, MD; 2Johns Hopkins University School of Medicine, Baltimore, MD
Patient-derived xenograft (PDX) models maintain the complex intra-tumoral biology and heterogeneity of an intact malignancy, as well as the interplay with stromal components and other cells fluxing into the tumor environment. This intrinsic cross-talk between different elements of the tumor makes PDX models a superior tool for translational drug discovery research and personalized oncology studies. Champions PDX models were originally developed for personalizing cancer treatments through the different Champions clinical programs. These models accurately reflect the population of patients enrolling in clinical trials. We describe herein our extensive TumorBank of PDX models, a valuable resource for translational oncology research to predetermine target populations for intervention with novel therapeutics in specific cancer subtypes.
Tumor tissue from over 950 patients with a variety of primary and metastatic solid malignancies, across all ages and ethnicities and encompassing both treatment-naïve and heavily-pretreated individuals, has been implanted into immunodeficient mice with successful engraftment observed in ~72% of cases. Comprehensive and translational-relevant clinical annotations have been maintained for these PDX models, including patient demographics, disease stage, anatomic location, tumor grade and histology, and treatment history.
Importantly, whole exome and RNA sequencing, tissue histopathology, and protein immunohistochemistry have all been applied to 297 of these models. Finally, 70 of the models were screened against the corresponding patient’s treatment used in the clinic, demonstrating a sensitivity of 98%, specificity of 76%, positive predictive value of 89% and negative predictive value of 96%. This wealth of information can be accessed through the Champions TumorGraft Database. The combination of extensive molecular and clinical annotation, together with opportunities for unlimited prospective preclinical testing, makes Champions TumorBank a pioneering resource for pharmaceutical companies seeking to identify target populations for therapeutic intervention.