What is the role of Hedgehog (Hh) pathway inhibitors in the treatment of basal cell carcinoma (BCC)?

Updated: Mar 02, 2020
  • Author: Robert S Bader, MD; Chief Editor: William D James, MD  more...
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Answer

A Hedgehog (Hh) pathway inhibitor can be used to treat patients with locally advanced BCC who are not candidates for surgery or radiation therapy, or whose disease has recurred after surgery or radiation therapy, and those with metastatic BCC. [7] The FDA approved the first Hh pathway inhibitor, vismodegib (Erivedge), in January 2012, and the second, sonidegib (Odomzo), in July 2015. Those agents inhibit Smoothened (SMO), a transmembrane protein involved in Hh signal transduction.

In patients with metastatic BCC resistant to Hh pathway inhibitors, treatment with arsenic trioxide and itraconazole may offer some benefit. Ally and colleagues reported that three of five men with resistant metastatic BC responded to a regimen of intravenous arsenic trioxide 5 days, every 28 days, and oral itraconazole on days 6 to 28. Although some patients experienced stable disease for 3 months, none had tumor shrinkage; the authors suggest that continuous dosing may be required to fully inhibit the HH pathway and achieve clinical response in such cases. [73]


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