For reasons that are not well understood, kidney cancer is particularly prevalent in Texas. Translocation renal cell carcinoma (tRCC) is a challenging subtype of kidney cancer that predominantly affects children and adolescents and is uniformly lethal when metastatic. tRCC is an orphan disease without specific therapies, and therefore with devastating consequences for vulnerable patients and their families. Because of its relatively low frequency (compared to adult kidney cancer), tRCC remains understudied. A major barrier to progress has been the lack of animal models reproducing the features of human tRCC. Here, we propose to deploy a novel mouse model of tRCC we generated to provide insig...

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For reasons that are not well understood, kidney cancer is particularly prevalent in Texas. Translocation renal cell carcinoma (tRCC) is a challenging subtype of kidney cancer that predominantly affects children and adolescents and is uniformly lethal when metastatic. tRCC is an orphan disease without specific therapies, and therefore with devastating consequences for vulnerable patients and their families. Because of its relatively low frequency (compared to adult kidney cancer), tRCC remains understudied. A major barrier to progress has been the lack of animal models reproducing the features of human tRCC. Here, we propose to deploy a novel mouse model of tRCC we generated to provide insight into mechanisms of tRCC tumorigenesis and advance therapies. This model is based on the most common human translocation and the mice uniformly develop tRCC that faithfully recapitulates the human disease, including its aggressiveness. We will leverage these mice, along with state-of-the-art technologies, to determine how the reshuffled genes trigger tRCC and how they stimulate uncontrolled cell proliferation. In addition, we will test a drug that we would predict to have activity against tRCC based on our preliminary studies. This research addresses critical gaps in understanding and treating tRCC. By elucidating the mechanisms of tumorigenesis, and evaluating a novel therapeutic approach, this project has the potential to significantly advance the field. The successful completion of this project will provide fundamental insights into molecular mechanisms driving tRCC and establish a foundation for the development of new therapies for a currently untreatable and deadly disease.

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