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Fig. 4 | Acta Neuropathologica Communications

Fig. 4

From: Phase I and phase II sonidegib and vismodegib clinical trials for the treatment of paediatric and adult MB patients: a systemic review and meta-analysis

Fig. 4

Hedgehog signalling and SMO inhibitors action in MB. a. Hedgehog (Hh) proteins (Sonic, Indian, or Desert Hedgehog) bind to PTCH1 transmembrane protein. Binding to PTCH1 relieves inhibition of smoothened (SMO). Active SMO moves to cilium and promotes to release suppressor of fused (SUFU) inhibition of glioma-associated oncogene (GLI) proteins. Activated GLI proteins then translocate to the nucleus to affect transcription of SHH target genes (ie, GLI1, GLI2, PTCH1, PTCH2, and MYCN). Vismodegib and sonidegib bind to the extracellular domain of SMO, inhibiting downstream signalling. Most commonly mutations in MB associated with Hh pathway includes, mutations in PTCH1 (red star, favourable prognostic mutation), SMO and SUFU (brown star, worse prognostic mutations). b. SMO inhibitors inhibit Hh pathway signalling by preventing activation of SMO

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