Uveal Melanoma Patient-Derived Xenografts

The prognosis of uveal melanoma (UM) remains poor due to a high risk of metastatic disease. No effective therapies have been described for metastatic UM, and new therapies are needed to improve the outcome for these patients. To achieve this goal, new preclinical animal models are needed. Existing animal models, including genetically engineered mice and orthotopic xenograft models in immunodeficient animals, are inadequate for modelling human disease. In this review, we present the development and characterization of a large panel of UM patientderived xenografts (PDXs). Based on molecular features as identified in patient tumors, i.e. histopathological classification, specific gene mutations, as well as genomic and gene expression profiles, we show that PDXs closely resemble many important genetic and histological aspects of human UM with a remarkable stability over the course of their in vivo maintenance. Our techniques for establishing and maintaining primary UMs as xenograft tumors in immunodeficient mice provide a high degree of genetic conservation between the primary tumor and its xenograft over multiple in vivo passages. These models therefore represent a significant advance in the resources available for drug screening and studies of the pathogenesis of UM. (C) 2015 S. Karger AG, Basel