SMO and skin basal cell carcinoma: While tumors with documented HH activation caused by LOH of PTCH such as BCC have been described to respond to SMO inhibitors [43], there is mounting evidence showing that these inhibitors exhibit limited efficiency against tumors with non-canonical HH activation, e.g. due to mutations downstream of SMO, GLI amplification or activation of HH-interacting pathways such as the PI3K/AKT/mTOR cascade [13, 16, 44, 45].