Abstract
Basal cell caricnoma (BCC), the most common periocular magliancy, is treated with complete surgical excision. However, in patients not amenable to surgery or when surgical resection means loss of vital organs or disfiguring procedures due to locally advanced or metastatic disease, targeting the hedgehog pathway offers a novel treatment approach for such patients. Mutation in PTCH1 and SMO has been identified in patients with basal cell nevoid syndrome as well as in patients with sporadic BCC. Inhibition of SMO by vismodegib or sonidegib, the two sonic hedgehog inhibitor drugs approved by the Food and Drug Administration in the United States, has shown overall response rate for locally advanced and metastatic BCC around 50%. The most common side effects were muscle cramps, weight loss, fatigue, and lost appetite. Resistance to vismodegib has been attributed to mutation in SMO or activation of RAS/MAPK pathway. New research into dual inhibition aims to overcome this resistance and provide more lasting response.
Keywords: Hedgehog pathway, hedgehog inhibitors, basal cell carcinoma, targeted therapy, locally advanced BCC, vismodegib, sonidegib.
Current Pharmaceutical Design
Title:Targeting the Hedgehog Pathway for Locally Advanced and Metastatic Basal Cell Carcinoma
Volume: 23 Issue: 4
Author(s): Vivian T. Yin and Bita Esmaeli
Affiliation:
Keywords: Hedgehog pathway, hedgehog inhibitors, basal cell carcinoma, targeted therapy, locally advanced BCC, vismodegib, sonidegib.
Abstract: Basal cell caricnoma (BCC), the most common periocular magliancy, is treated with complete surgical excision. However, in patients not amenable to surgery or when surgical resection means loss of vital organs or disfiguring procedures due to locally advanced or metastatic disease, targeting the hedgehog pathway offers a novel treatment approach for such patients. Mutation in PTCH1 and SMO has been identified in patients with basal cell nevoid syndrome as well as in patients with sporadic BCC. Inhibition of SMO by vismodegib or sonidegib, the two sonic hedgehog inhibitor drugs approved by the Food and Drug Administration in the United States, has shown overall response rate for locally advanced and metastatic BCC around 50%. The most common side effects were muscle cramps, weight loss, fatigue, and lost appetite. Resistance to vismodegib has been attributed to mutation in SMO or activation of RAS/MAPK pathway. New research into dual inhibition aims to overcome this resistance and provide more lasting response.
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Cite this article as:
Yin T. Vivian and Esmaeli Bita, Targeting the Hedgehog Pathway for Locally Advanced and Metastatic Basal Cell Carcinoma, Current Pharmaceutical Design 2017; 23 (4) . https://dx.doi.org/10.2174/1381612822666161208100325
DOI https://dx.doi.org/10.2174/1381612822666161208100325 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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