In recent years, TFE3/IRS-1/PI3K/AKT/mTOR, as a potential dysregulated pathway in TFE3-tRCC, may serve as a therapeutic potential for vertical inhibition of such axis by using a dual PI3K/mTOR inhibitor for TFE3-tRCC patients [38]. Here, IRS1 is linked to renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.