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Hedgehog Signaling Pathway02:33

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Hedgehog Pathway Inhibition.

Aleksandar Sekulic1, Daniel Von Hoff2

  • 1Department of Dermatology, Mayo Clinic, Scottsdale, AZ 85259, USA.

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|February 27, 2016
PubMed
Summary
This summary is machine-generated.

The hedgehog (Hh) signaling pathway is crucial in basal cell carcinoma (BCC). Targeted therapies like vismodegib and sonidegib inhibit Smoothened (SMO) and are approved for advanced BCC.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Aberrant activation of the hedgehog (Hh) signaling pathway is a hallmark of basal cell carcinoma (BCC).
  • This pathway plays a critical role in the development and progression of BCC.
  • Understanding Hh pathway dysregulation is key to developing effective treatments.

Purpose of the Study:

  • To review the role of the hedgehog (Hh) signaling pathway in basal cell carcinoma (BCC).
  • To discuss the mechanism of action of Smoothened (SMO) inhibitors.
  • To highlight the clinical applications of approved SMO inhibitors in BCC treatment.

Main Methods:

  • Literature review of studies on hedgehog signaling in BCC.
  • Analysis of clinical trial data for SMO inhibitors.
  • Review of regulatory approvals for BCC therapies.

Main Results:

  • The hedgehog (Hh) signaling pathway is frequently hyperactivated in basal cell carcinomas (BCC).
  • Vismodegib and sonidegib are targeted therapies that inhibit Smoothened (SMO), a key component of the Hh pathway.
  • Both vismodegib and sonidegib are approved for treating locally advanced BCC (laBCC).

Conclusions:

  • Targeted inhibition of the Smoothened (SMO) component of the hedgehog (Hh) pathway is an effective strategy for basal cell carcinoma (BCC) treatment.
  • Vismodegib and sonidegib represent significant advancements in managing locally advanced and metastatic BCC.
  • Continued research into Hh pathway inhibitors may offer further therapeutic options for BCC patients.