Abstract
The Hedgehog inhibitors are promising alternative for patients with advanced basal cell carcinoma that are not amenable to radiotherapy or surgery. Sonidegib, also known as LDE225, is an orally available SMO antagonist that was recently approved by the US FDA for the treatment of patients with locally advanced basal cell carcinoma. This article will provide an overview of the pharmacology and pharmacokinetics of sonidegib and in-depth analysis of the BOLT trial with additional data from the 12-month update. The present challenges associated with Hedgehog inhibitors will also be discussed.
Keywords:
BOLT trial; basal cell carcinoma; sonidegib.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology
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Biphenyl Compounds / therapeutic use*
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Carcinoma, Basal Cell / drug therapy*
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Carcinoma, Basal Cell / metabolism
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Carcinoma, Basal Cell / pathology*
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Clinical Trials as Topic
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Follow-Up Studies
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Hedgehog Proteins / antagonists & inhibitors
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Humans
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Mice
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Pyridines / chemistry
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Pyridines / pharmacology
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Pyridines / therapeutic use*
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Signal Transduction / drug effects
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology*
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Smoothened Receptor / antagonists & inhibitors
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Treatment Outcome
Substances
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Antineoplastic Agents
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Biphenyl Compounds
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Hedgehog Proteins
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Pyridines
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Smoothened Receptor
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sonidegib