Figure 3.

Sonic hedgehog signaling is crucial during normal development of cerebellum, and its dysregulation leads to medulloblastoma development. Mutations of PTCH1,SMO, and SUFU, or amplification of GLI2 contribute to downstream activation of Hedgehog signaling targets. Several small molecule inhibitors of SMO, such as sonidegib (LDE‐225) or vismodegib (GDC‐0449), are being investigated as potential targeted therapies in clinical trials. Mutations downstream of SMO render such inhibitors ineffective. Itraconazole has the ability to inhibit SMO activation including some SMO mutations that confer resistance to SMO inhibitors, and arsenic trioxide inhibits GLI2 ciliary accumulation.