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Understand metastasis of uveal melanoma in vivo via novel mouse models

Xiaonan Xu, MD, PhD

Award Type Career Development Award
Institution Moffitt Cancer Center
Uveal melanoma (UM) is the most common eye cancer in adults which originates from pigmented cells in the uvea of the eye. The major challenge in UM treatment is the high frequency of metastasis. Even with successful local treatment of the primary tumor in the early stage, up to half of UM patients will eventually develop distant metastasis, primarily to the liver. However, there currently is no available therapy to prevent or treat UM metastasis, and therapies that have proven effective in cutaneous melanoma such as targeted therapy and immunotherapy have little or no success in UM. This is because UM has a unique genetic landscape. Genetically engineered mouse models (GEMM) are among the best tools to recapitulate cancer initiation and progression. Therefore, I developed a novel UM specific GEMM that not only recapitulates human uveal nevus hyperplasia and melanogenesis, but also acts as a versatile platform for gene editing and metastasis tracking. In this project, I aim to unravel the mechanisms underlying UM metastasis using this novel UM mouse model.