Identifying Therapeutic Targets for MiT Associated Pediatric Cancers
The long-term goal of this research is to identify therapies for the aggressive translocation renal cell carcinomas that affect children and young adults. A majority of these tumors present at advanced stage and half of the patients with translocation renal cell carcinoma will parish from the cancer. Thus, there is an urgent need to define therapeutic strategies to treat these cancers. To accomplish this goal, we propose to study the microphthalmia (MiT) family genes TFE3, TFEB, and MITF that are known to drive these cancers. These genes are turned on in these cancers, but how these genes promote kidney cancer continues to remain unclear. Therefore, we have generated and are developing novel genetic tools to dissect the mechanism these genes use to cause cancer. We propose to characterize how these genes convert otherwise normal cells into cells that become cancer. We also plan to use our unique genetic tools to identify other changes that occur in these tumors that cooperate to drive cancer. Identifying the changes required to develop these kidney tumors will provide new avenues for cancer therapy. Finally, we will develop a preclinical model of translocation renal cell carcinoma to test these new therapeutic approaches. Accomplishing these aims will identify new strategies for eradicating these deadly tumors.