Chasing the Hedgehog: aPKC as a Potential Target in BCC

The role of the hedgehog (HH) pathway in basal cell carcinoma (BCC) has been well established, and the pathway is the objective of the first targeted therapy for aggressive and metastatic BCC. The PTCH gene is frequently inactivated in BCC, which leads to high HH pathway signaling, driving cellular proliferation through activation of SMO (smoothened) and GLI transcription factors. Vismodegib, recently approved for BCC, acts by inhibiting SMO. As expected, vismodegib resistance has been observed, most often as a result of pathway reactivation.

Atwood and colleagues attempted to identify additional druggable targets in the HH pathway by looking for binding partners of MIM, a scaffold protein that regulates HH signaling. They identified atypica…