SMO and skin basal cell carcinoma: SMOi provide clear clinical benefit to BCC patients, though rapid development of SMOi resistance and a priori insensitivity to SMO antagonists limit the therapeutic efficacy of SMO targeting.11 The lack of efficacy can, at least in part, be attributed to the many possibilities of malignant cells to activate GLI transcription factors in a noncanonical (SMO‐independent) manner.