Interestingly, and in contrast with what it is usually observed in other types of cancer, GLI1 deregulation in Ewing sarcoma is independent of Shh since its activation did not produce phenotypic changes nor did a pharmacological blockage of SMO using cyclopamine (an inhibitor of Shh signaling by direct binding to SMO) (45). Here, SHH is linked to Ewing sarcoma.