1. Targeting Hedgehog signaling pathway: Paving the road for cancer therapy
- Author
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Diana Gulei, Samira Shirooie, Seyed Mohammad Nabavi, Davide Barreca, Ammad Ahmad Farooqi, Ipek Süntar, Ali Salaritabar, Maria Daglia, Behrad Darvish, Seyed Fazel Nabavi, Ilkay Erdogan Orhan, Kasi Pandima Devi, Azadeh Manayi, Antoni Sureda, Ahmad Reza Dehpour, Ioana Berindan-Neagoe, Farzaneh Hadjiakhoondi, Salaritabar, A., Berindan-Neagoe, I., Darvish, B., Hadjiakhoondi, F., Manayi, A., Devi, K. P., Barreca, D., Orhan, I. E., Suntar, I., Farooqi, A. A., Gulei, D., Nabavi, S. F., Sureda, A., Daglia, M., Dehpour, A. R., Nabavi, S. M., and Shirooie, S.
- Subjects
0301 basic medicine ,Angiogenesis ,Cancer therapy ,Antineoplastic Agents ,Smad Proteins ,Hedgehog signaling ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Neoplasms ,Anticancer Therapy, Embryonic development, Hedgehog signaling, Self-renewal ,Animals ,Humans ,Hedgehog Proteins ,Receptors, Platelet-Derived Growth Factor ,Molecular Targeted Therapy ,Hedgehog ,Pharmacology ,Receptors, Notch ,Anticancer therapy ,Hedgehog signaling pathway ,Cell biology ,Crosstalk (biology) ,030104 developmental biology ,030220 oncology & carcinogenesis ,Embryonic development ,Self-renewal ,Stem cell ,Signal transduction ,Homeostasis ,Signal Transduction - 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.
- Published
- 2019