Abstract
Dependence of basal cell carcinomas and medulloblastomas on the Hedgehog pathway provides an opportunity for targeted or "personalized" therapy. The recent effectiveness and FDA approval of the first Smoothened inhibitors validates this class of agents, but has revealed drug-resistant tumor variants that bypass Smoothened inhibition. Here, we summarize the effectiveness of Hedgehog pathway inhibitors and highlight promising areas for the development of next generation drug antagonists for Hedgehog-dependent cancers.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anilides / pharmacology
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Anilides / therapeutic use
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Antineoplastic Agents / therapeutic use
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Carcinoma, Basal Cell / drug therapy*
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Carcinoma, Basal Cell / metabolism
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Cerebellar Neoplasms / drug therapy
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Cerebellar Neoplasms / metabolism
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Drug Resistance, Neoplasm
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Hedgehog Proteins / antagonists & inhibitors*
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Hedgehog Proteins / metabolism*
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Humans
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Medulloblastoma / drug therapy*
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Medulloblastoma / metabolism
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Pyridines / pharmacology
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Pyridines / therapeutic use
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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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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Smoothened Receptor
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Transcription Factors / antagonists & inhibitors
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Veratrum Alkaloids / pharmacology
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Veratrum Alkaloids / therapeutic use
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Zinc Finger Protein GLI1
Substances
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Anilides
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Antineoplastic Agents
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GLI1 protein, human
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Hedgehog Proteins
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HhAntag691
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Pyridines
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Receptors, G-Protein-Coupled
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SMO protein, human
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Smoothened Receptor
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Transcription Factors
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Veratrum Alkaloids
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Zinc Finger Protein GLI1
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cyclopamine