Beyond cyclopamine: Targeting Hedgehog signaling for cancer intervention

Arch Biochem Biophys. 2024 Apr:754:109952. doi: 10.1016/j.abb.2024.109952. Epub 2024 Mar 1.

Abstract

Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological setting, it is associated with oncogenesis and is responsible for disease progression and poor clinical outcomes. Hedgehog signaling mediates downstream actions via Glioma Associated Oncogene Homolog (GLI) transcription factors. Inhibiting Hh signaling is an important oncological strategy in which inhibitors of the ligands SMO or GLI have been looked at. This review briefly narrates the Hh ligands, signal transduction, the target genes involved and comprehensively describes the numerous inhibitors that have been evaluated for use in various neoplastic settings.

Keywords: GLI; Hedgehog signaling pathway; PTCH; SMO; Sonidegib; Vismodegib.

Publication types

  • Review

MeSH terms

  • Hedgehog Proteins*
  • Humans
  • Neoplasms* / drug therapy
  • Signal Transduction / genetics
  • Veratrum Alkaloids

Substances

  • Hedgehog Proteins
  • cyclopamine
  • Veratrum Alkaloids