In this study multiple TFE3-RCC tumor-derived cell lines representing different TFE3 fusions were utilized to generate in vitro and in vivo preclinical data supporting the efficacy of PI3K/mTOR inhibitor NVP-BGT226, transcription inhibitor Mithramycin A, and GPNMB-targeted antibody-drug conjugate CDX-011 as potential therapeutic options for treating advanced MiT-RCC. The gene discussed is TFE3; the disease is renal cell carcinoma.