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We aimed to characterise the response of locally advanced basal cell carcinoma (BCC) to systemic treatment with Vismodegib, a Hedgehog pathway inhibitor, by changes in the expression levels of Hedgehog pathway genes. Data were collected prospectively on 12 patients treated systemically for locally advanced BCC. Biopsy samples taken on admission and after treatment cessation were analysed pathologically and with the NanoString nCounter system to quantify the expression of 40 Hedgehog signaling pathway genes. Findings were compared before and after treatment, between complete and partial responders, and with localised BCC samples from 22 patients. Sixteen Hedgehog pathway genes changed significantly from before to after treatment.  GAS1  was the only gene with a significantly different expression at baseline between complete responders (6 patients) and partial responders (4 patients) to Vismodegib ( P  = 0.014). GAS,  GLIS2  and  PRKACG 1 showed different expression before treatment between the locally advanced and localised BCCs. The baseline expression level of  GAS1  appears to be predictive of the response of locally advanced BCC to systemic Vismodegib treatment. A change in expression of many Hedgehog pathway genes, albeit expected by the known activity of Vismodegib, may nevertheless serve as an indicator of the response potential of the tumour.

Gene-Related Response of Basal Cell Carcinoma to Biologic Treatment with Vismodegib