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

Updated: Mar 23, 2021
  • Author: Robert S Bader, MD; Chief Editor: William D James, MD  more...
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A Hedgehog pathway inhibitor (HHI) 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 HHI pathway inhibitor, vismodegib (Erivedge), in 2012 and the second, sonidegib (Odomzo), in 2015. Those agents inhibit Smoothened (SMO), a transmembrane protein involved in Hedgehog pathway signal transduction.

In patients with metastatic BCC resistant to HHIs, 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 Hedgehog pathway and achieve clinical response in such cases. [74]

In February 2021, the first immunotherapy, cemiplimab (Libtayo), was fully approved for locally advanced BCC and granted accelerated approval for metastatic BCC previously treated with an HHI or for whom an HHI is not appropriate.

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