Substituting One Smoothened Inhibitor for Another Did Not Forestall Resistance

Smoothened (SMO) inhibitors are used to treat advanced basal cell carcinomas (BCCs). Vismodegib is a first-line therapy of this type FDA approved for locally advanced and metastatic BCCs. However, despite complete or partial remission in some patients, more than half of those treated have no response to vismodegib, and more than 20% of initial responders develop resistance.

Danial and colleagues studied the response of advanced BCCs resistant to vismodegib to the novel SMO inhibitor sonidegib. Nine patients with such resistant tumors were treated. Primary resistance was stable or progressive disease, and secondary resistance was progressive disease after some initial response. After a median treatment period of 6 weeks with sonidegib, none o…