Vismodegib is approved for treatment of locally advanced and metastatic basal cell carcinoma. Its mechanism of action is:

• A BRAF V600E kinase inhibitor
• B Hedgehog pathway inhibitor — blocks Smoothened (SMO) receptor ✓
• C PD-1 checkpoint inhibitor enhancing T-cell cytotoxicity
• D EGFR inhibitor reducing RAS-MAPK signalling

Explanation

Vismodegib and sonidegib are Hedgehog pathway inhibitors that block the Smoothened (SMO) transmembrane protein, preventing transcription of GLI1/GLI2 target genes that drive BCC growth. Constitutive Hedgehog pathway activation in BCC is most commonly due to loss-of-function mutations in PTCH1 (tumour suppressor) or activating mutations in SMO. BRAF inhibitors (vemurafenib, dabrafenib) are used for BRAF-mutant melanoma; PD-1 inhibitors (cemiplimab) are approved for advanced cutaneous SCC.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.