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Smoothened Inhibitors in Cancer

  • Martial Ruat
  • Lucile Hoch
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Part of the Topics in Medicinal Chemistry book series (TMC, volume 16)

Abstract

Smoothened (Smo) inhibitors are under intense development for the treatment of cancers linked to abnormal Hedgehog (Hh) signaling. The first inhibitor (vismodegib) was introduced in clinics for basal cell carcinoma and medulloblastomas associated with activating mutations of Hh signaling. In contrast, disappointing data are reported for cancers related to ligand overexpression. Here, we review recent preclinical and clinical data on the potential therapeutic importance of Smo and highlight the complexity of Smo pharmacology and its clinical implications.

Keywords

Cancer stem cell Hedgehog Medulloblastoma Resistance 

Abbreviations

7TM

7-Transmembrane domain

BCC

Basal cell carcinoma

Gli1–3

Glioma-associated oncogenes 1–3

GPCR

G-protein-coupled receptor

Hh

Hedgehog

PKA

Protein kinase A

Ptc

Patched

Smo

Smoothened

Sufu

Suppressor of fused

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Martial Ruat
    • 1
  • Lucile Hoch
    • 1
  1. 1.Signal Transduction and Developmental Neuropharmacology Team, Department of Molecules and Circuits, CNRS, UMR 9197, Neurosciences Paris-Saclay InstituteParis Sud UniversityGif-sur-YvetteFrance

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