Hedgehog signaling in basal cell carcinoma

• Basal cell carcinoma is the most common cancer type and its incidence rate is increasing.
• Mutations that occur in BCC in hedgehog pathway genes primarily involve the genes encoding patched homolog and smoothened homolog.
• The Hedgehog pathway plays a crucial role in patterning and organogenesis during early development.
• Hedgehog pathway inhibitors not only suppress BCC progression but also promote acquired immune responses.

Basal cell carcinoma (BCC), the most common type of skin cancer, is occasionally aggressive with deep invasion, destruction of adjacent structures, recurrence and, on very rare occasions, regional and distant metastases. Mutations that occur in BCC in hedgehog (Hh) pathway genes primarily involve the genes encoding patched homolog (PTCH) and smoothened homolog (SMO). Several animal models have demonstrated the functional relevance of genetic alterations in the Hh pathway during tumorigenesis. Recently, targeted therapy has become available both commercially and in the context of human clinical trials. Interestingly, Hh pathway inhibitors not only suppress BCC progression but also promote acquired immune responses. Since immune responses are crucial for long-term tumor control, new clinical trials, such as those involving a combination of Hh inhibitors with immune modifiers, are needed to supplement standard methods of tumor control.