Hedgehog- and mTOR-targeted therapies for advanced basal cell carcinomas

Future Oncol. 2015 Nov;11(22):2997-3002. doi: 10.2217/fon.15.181. Epub 2015 Oct 5.

Abstract

Basal cell carcinomas (BCCs) are the most frequent human cancer. Over 90% of all BCCs have a mutation in PTCH1 or smoothened, two conducting proteins of the Hedgehog pathway. They rarely progress deeply and metastasize; however, if they do, these advanced basal cell carcinoma become amenable to treatment by inhibiting the Hedgehog and the P13K-mTOR pathways. Such innovative drugs include vismodegib, cyclopamine, itraconazole, everolimus and a few other agents that are in early clinical development.

Keywords: Desert Hedgehog; EGF; Hedgehog; Indian Hedgehog; NF-κB; PTCH1; SMO; Sonic Hedgehog; TGF; basal cell carcinoma; cancer stem cell; cyclopamine; cytotoxic chemotherapy; everolimus; hereditary basal cell nevus syndrome; itraconazole; metastasis; protein kinase; therapy resistance; vismodegib.

Publication types

  • Review

MeSH terms

  • Anilides / pharmacology
  • Anilides / therapeutic use
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Drug Resistance, Neoplasm
  • Everolimus / pharmacology
  • Everolimus / therapeutic use
  • Hedgehog Proteins / antagonists & inhibitors*
  • Hedgehog Proteins / metabolism
  • Humans
  • Itraconazole / pharmacology
  • Itraconazole / therapeutic use
  • Molecular Targeted Therapy*
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Smoothened Receptor
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Veratrum Alkaloids / pharmacology
  • Veratrum Alkaloids / therapeutic use

Substances

  • Anilides
  • Hedgehog Proteins
  • HhAntag691
  • Pyridines
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor
  • Veratrum Alkaloids
  • Itraconazole
  • Everolimus
  • TOR Serine-Threonine Kinases
  • cyclopamine