Targeting Hedgehog Signaling Pathway: Paving the Road for Cancer Therapy Publisher Pubmed



Salaritabar A¹ ; Berindanneagoe I^{2, 3, 4} ; Darvish B⁵ ; Hadjiakhoondi F⁶ ; Manayi A⁶ ; Devi KP⁷ ; Barreca D⁸ ; Orhan IE⁹ ; Suntar I⁹ ; Farooqi AA¹⁰ ; Gulei D¹ ; Nabavi SF¹¹ ; Sureda A¹² ; Daglia M¹³ Show All Authors
Source: Pharmacological Research Published:2019

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. © 2019 Elsevier Ltd