Vismodegib, itraconazole and sonidegib as hedgehog pathway inhibitors and their relative competencies in the treatment of basal cell carcinomas

Crit Rev Oncol Hematol. 2016 Feb;98:235-41. doi: 10.1016/j.critrevonc.2015.11.006. Epub 2015 Nov 21.

Abstract

The advent of more sophisticated studies published has clarified the understating of the root cause of various skin cancers or basal cell carcinomas (BCCs). The remarkable role is played by the comprehensive work done on unraveling the mechanism controlling the function of hedgehog (Hh) pathway. The defective Hh pathway has been found as the major cause for BCCs as activated Hh signaling within primary cilia plays a key role in the pathogenesis of BCCs. The BCC accounts for up to 40% of all cancers in the US, with growing incidences in other countries as well. Thus, it is considered to be utmost important by the researchers all over the world developing drugs for the treatment of skin cancers targeting Hh pathway. Fewer drugs like vismodegib, itraconazole and sonidegib have shown promising results inhibiting the awry function of Hh pathway resulting in treatment of different forms of skin cancers. These drugs have shown positive results but failed to prove their potential as expected. Vismodegib and sonidegib are better but fail in case of resistant tumors. This review article describes the mechanism of actions of these Hh pathway inhibitors and provides the rationale for their effectiveness/non-effectiveness for the treatment of metastatic or locally advanced BCC.

Keywords: Basal cell carcinoma; Hedgehog pathway; Itraconazole; Metastasis; Sonidegib; Vismodegib.

Publication types

  • Review

MeSH terms

  • Anilides / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biphenyl Compounds / administration & dosage
  • Carcinoma, Basal Cell / drug therapy*
  • Drug Resistance, Neoplasm
  • Hedgehog Proteins / antagonists & inhibitors*
  • Hedgehog Proteins / physiology
  • Humans
  • Itraconazole / administration & dosage
  • Pyridines / administration & dosage
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*

Substances

  • Anilides
  • Biphenyl Compounds
  • Hedgehog Proteins
  • HhAntag691
  • Pyridines
  • sonidegib
  • Itraconazole