Targeting Hedgehog signaling pathway: Paving the road for cancer therapy

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...

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Published inPharmacological research Vol. 141; pp. 466 - 480
Main Authors Salaritabar, Ali, Berindan-Neagoe, Ioana, Darvish, Behrad, Hadjiakhoondi, Farzaneh, Manayi, Azadeh, Devi, Kasi Pandima, Barreca, Davide, Orhan, Ilkay Erdogan, Süntar, Ipek, Farooqi, Ammad Ahmad, Gulei, Diana, Nabavi, Seyed Fazel, Sureda, Antoni, Daglia, Maria, Dehpour, Ahmad R., Nabavi, Seyed Mohammad, Shirooie, Samira
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.03.2019
Subjects
Anticancer therapy
Embryonic development
Hedgehog signaling
Self-renewal
Embryonic development
Hedgehog signaling
Self-renewal
Anticancer therapy
Online AccessGet full text
ISSN1043-6618
1096-1186
1096-1186
DOI10.1016/j.phrs.2019.01.014

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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.
AbstractList 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.
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.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.
Author Manayi, Azadeh
Sureda, Antoni
Darvish, Behrad
Nabavi, Seyed Fazel
Hadjiakhoondi, Farzaneh
Orhan, Ilkay Erdogan
Gulei, Diana
Salaritabar, Ali
Nabavi, Seyed Mohammad
Berindan-Neagoe, Ioana
Daglia, Maria
Shirooie, Samira
Devi, Kasi Pandima
Barreca, Davide
Farooqi, Ammad Ahmad
Süntar, Ipek
Dehpour, Ahmad R.
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– sequence: 8
  givenname: Ilkay Erdogan
  surname: Orhan
  fullname: Orhan, Ilkay Erdogan
  organization: Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330, Ankara, Turkey
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  givenname: Ammad Ahmad
  surname: Farooqi
  fullname: Farooqi, Ammad Ahmad
  organization: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, 54000, Pakistan
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  surname: Sureda
  fullname: Sureda, Antoni
  organization: Research Group on Community Nutrition and Oxidative Stress (NUCOX) and CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), University of Balearic Islands, Palma de Mallorca, E-07122, Balearic Islands, Spain
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  surname: Daglia
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  organization: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, 27100, Pavia, Italy
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ISSN 1043-6618
1096-1186
IngestDate Fri Sep 05 09:49:38 EDT 2025
Mon Jul 21 06:06:29 EDT 2025
Thu Apr 24 22:57:02 EDT 2025
Tue Jul 01 03:33:42 EDT 2025
Fri Feb 23 02:19:14 EST 2024
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Keywords Embryonic development
Hedgehog signaling
Self-renewal
Anticancer therapy
Language English
License Copyright © 2019 Elsevier Ltd. All rights reserved.
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Snippet The Hedgehog pathway is essential for embryonic development but also for tissue and organ homeostasis in adult organisms. Activation of this pathway leads to...
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SubjectTerms Anticancer therapy
Embryonic development
Hedgehog signaling
Self-renewal
Title Targeting Hedgehog signaling pathway: Paving the road for cancer therapy
URI https://dx.doi.org/10.1016/j.phrs.2019.01.014
https://www.ncbi.nlm.nih.gov/pubmed/30639373
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