VHL and nonpapillary renal cell carcinoma: Though activations of Hh signaling have been associated with poor progression of ccRCC [47–49], we firstly provide evidence that Hh pathway activation in VHL-wt ccRCC depends on the primary cilia and VHL-wt ccRCC is more susceptible to Hh inhibitors than VHL-mut ccRCC, suggesting that targeting Hh signaling may be an attractive therapeutic strategy for VHL-wt ccRCC.