Hedgehog inhibitors, more accurately known as smoothened inhibitors (SIs), were introduced for the treatment of basal cell carcinoma (BCC) with much success.1 The clinical data supported the intriguing rationale of interfering with a tumor driver (overactive Sonic Hedgehog signaling in BCC) that was identified 20 years ago. Beyond the well-established surgical or conservative (radiotherapy) treatment options, treatment with SIs now represents a novel avenue the dermato-oncologist can take when surgery or radiotherapy of BCC is contraindicated.2 This extension of the therapeutic armamentarium for advanced BCC, which is currently used in patients with highly advanced tumors or basal cell nevus syndrome, has also suggested using vismodegib or sonidegib treatment in a neoadjuvant setting. However, neoadjuvant therapy would be precluded by the development of secondary resistance to vismodegib, which is mediated in the vast majority of cases by secondary mutations in smoothened.3,4
Rübben A, Hilgers R, Leverkus M. Hedgehog Blockade for Basal Cell Carcinoma: Coming at a (Secondary Neoplastic) Price. JAMA Dermatol. 2016;152(5):521–523. doi:10.1001/jamadermatol.2015.5239
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