Current Status of Hedgehog Signaling Inhibitors

Abstract

Abstract: The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological pro-cesses such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transfor-mation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive acti-vation, can contribute to the development of various diseases during different stages of biogenesis and development. Moreover, it has been linked to unfavorable outcomes in several human can-cers, including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast can-cer. Hence, the presence of mutations and excessive activation of the Hh pathway presents obsta-cles and constraints in the realm of cancer treatment. Extant research has demonstrated that small molecule inhibitors are regarded as the most effective therapeutic approaches for targeting the Hh pathway in contrast to traditional chemotherapy and radiotherapy. Consequently, this review fo-cuses on the present repertoire of small molecule inhibitors that target various components of the Hh pathway, including Hh ligands, Ptch receptors, Smo transmembrane proteins, and Gli nuclear transcription factors. This study provides a comprehensive analysis of small molecules' structural and functional aspects in the preclinical and clinical management of cancer. Additionally, it elu-cidates the obstacles encountered in targeting the Hh pathway for human cancer therapy and pro-poses potential therapeutic approaches.