Hedgehog pathway inhibition and the race against tumor evolution.
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.
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Scott X
SX
Atwood
Anne Lynn S
AL
Chang
Anthony E
AE
Oro
D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014704:Veratrum Alkaloids / Q000494:pharmacology / Q000627:therapeutic use; D000071676:Zinc Finger Protein GLI1
D000813:Anilides; D000970:Antineoplastic Agents; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine