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

Amir Sternfeld, Shirel Rosenwasser-Weiss, Gur Ben-Yehuda, Hila Kreizman Shefer, Moran Friedman-Gohas, Iftach Yassur, Gil Tauber, Jacob Bejar, Asaf Olshinka, Yoav Vardizer, Dean Ad El, Nitza Goldenberg-Cohen

Research output: Contribution to journalArticlepeer-review

Abstract

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 PRKACG1 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.

Original languageEnglish
Article number1244
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2020
Externally publishedYes

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