Targeting Hedgehog signaling pathway: Paving the road for cancer therapy.

Abstract

The Hedgehog pathway is essential for embryonic development but also for tissue and organ homeostasis in adult organisms. Activation of this pathway leads to the expression of target genes involved in proliferation, angiogenesis and stem cell self-renewal. Moreover, abnormal persistence of Hedgehog signaling is directly involved in a wide range of human cancers. Development of novel strategies targeting the Hedgehog pathway has become a subject of increased interest in anticancer therapy. These data are sustained by pre-clinical studies demonstrating that Hedgehog pathway inhibitors could represent an effective strategy against a heterogeneous panel of malignancies. Limited activity in other tumor types could be explained by the existence of crosstalk between the Hedgehog pathway and other signaling pathways that can compensate for its function. This review describes the Hedgehog pathway in detail, with its physiological roles during embryogenesis and adult tissues, and summarizing the preclinical evidence on its inhibition, the crosstalk between Hedgehog and other cancer-related pathways and finally the potential therapeutic effects of emerging compounds.

• Authors: Ali Salaritabar, Ioana Berindan-Neagoe, Behrad Darvish, Farzaneh Hadjiakhoondi, Azadeh Manayi, Kasi Pandima Devi, Davide Barreca, Ilkay Erdogan Orhan, Ipek Süntar, Ammad Ahmad Farooqi, Diana Gulei, Seyed Fazel Nabavi, Antoni Sureda, Maria Daglia, Ahmad R Dehpour, Seyed Mohammad Nabavi, Samira Shirooie
• Journal: Pharmacological research (Pharmacol Res) Vol. 141 Pg. 466-480 (03 2019) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 30639373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hedgehog Proteins
• Receptors, Notch
• Smad Proteins
• Transforming Growth Factor beta
• Receptors, Platelet-Derived Growth Factor

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Hedgehog Proteins (metabolism)
• Humans
• Molecular Targeted Therapy (methods)
• Neoplasms (drug therapy, metabolism, pathology)
• Receptors, Notch (metabolism)
• Receptors, Platelet-Derived Growth Factor (metabolism)
• Signal Transduction (drug effects)
• Smad Proteins (metabolism)
• Transforming Growth Factor beta (metabolism)