The unique profile of ccRCC tumors expressing mutant VHL stable expression of HIFs, and upregulated oncogenic miRNAs, and downregulated tumor suppressor miRNAs make it an excellent model for proof-of-concept that modulation of the expression levels and functions of these markers by therapeutically effective doses and schedules of Se may offer the potential to circumvent drug resistance, and may offer a new and novel clinical approach for the treatment of cancer. This evidence concerns the gene VHL and nonpapillary renal cell carcinoma.