The therapeutic biomarker PIK3R2 was identified for aggressive Xp11.2 tRCC, and the efficacy of a novel therapy (i.e., the PI3K pathway inhibitor LY294002) was evaluated according to this biomarker. This evidence concerns the gene PIK3R2 and renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.