Abstract
Hedgehog (HH) signaling pathway plays vital roles in controlling embryonic cell fate and homeostatic, and becomes dormant in mature individuals, aberrant activation of HH signaling pathway is involved in a number of human cancers. Smoothened (SMO), a vital transducer of HH signaling pathway, attracts significant attentions in HH signaling pathway-related cancer therapy. The approval of SMO antagonists vismodegib proves that SMO is a promising therapeutic target, and a number of SMO antagonists are reported since then. However, high incidence of tumor recurrence with the clinical application of vismodegib urges exploring of novel drugs with antiresistance profiles. This review provides an overview of SMO mutations reported in the literature, crystal structures of SMO, as well as reported antagonists with antiresistance profiles.
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