Vismodegib Resistance in Basal Cell Carcinoma: Not a Smooth Fit Todd W. Ridky, George Cotsarelis  Cancer Cell  Volume 27, Issue 3, Pages 315-316 (March 2015) DOI: 10.1016/j.ccell.2015.02.009 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 HH Signaling Pathway BCC is driven by activation of the HH pathway. Normally, Patched signaling inhibits Smoothened, which prevents Smoothened from activating Gli transcription factors that transcribe HH target genes. Gli is also inhibited by Supressor of fused (SUFU) and activated by aPKC-ι/λ. During development, and in a few adult tissues, HH binds to Patched, releasing its inhibitory activity on SMO and thereby activating the pathway. BCC is driven most commonly by inactivating mutations in PTCH, although activating mutations in SMO or Gli can also serve as oncodrivers. Tumor resistance to vismodegib usually results from SMO mutations that prevent drug binding. Targeting the pathway downstream may therefore be a useful therapeutic strategy. Red, elements that normally suppress HH signaling; green, elements that activate the pathway; yellow, pharmacologic agents that may be useful for primary or vismodegib resistant BCC. Cancer Cell 2015 27, 315-316DOI: (10.1016/j.ccell.2015.02.009) Copyright © 2015 Elsevier Inc. Terms and Conditions