Models and discovery strategies for new therapies of retinoblastoma.

Introduction: Retinoblastoma is the most common primary intraocular malignancy in children. Treatment success approaches 100% at specialized centers with globe-salvaging modalities. Primary management of retinoblastoma consists of chemoreduction with local consolidation, although newer techniques include local delivery via intra-arterial chemotherapy, periocular, or intravitreal injection. Animal models have played an integral role in the understanding of retinoblastoma tumorigenesis and have contributed to the development of globe-salvaging treatments.

Areas Covered: This review focuses on the use of models and discovery strategies on translational research in retinoblastoma. The article reviews gene expression profiling, knockout models, and transgenic animal models. In addition, the review discusses translational applications of hyperthermia, chemotherapy (systemic and local delivery), radiation therapy, and novel targets such as hypoxia, angiogenesis, cellular metabolism, and tumor suppressor functions.

Expert Opinion: Retinoblastoma treatment success has been driven by translational research using novel animal models and discovery strategies. Future developments require further understanding of the unique genetic events that result in tumor growth and development, as well as an understanding of the complex interactions of tumor cells with the local tumor microenvironment and how this affects tumor growth, metastasis, and response to treatment.