Title:Current Status of Hedgehog Signaling Inhibitors
Volume: 24
Issue: 3
Author(s): Xiaotang Wang, Tian Wang, Xiaona Song, Jiping Gao, Guoqiang Xu, Yunhui Ma and Guohua Song*
Affiliation:
- Laboratory Animal Center, Shanxi Medical University, No 56, Xinjian South Rd, Taiyuan, 030001, China
- Department of Basic Medical Sciences, Shanxi Medical University, No 56, Xinjian South Rd, Taiyuan, 030001, China
- School and Hospital of Stomatology, Shanxi Medical University, No 56, Xinjian South Rd, Taiyuan, 030001, China
Keywords:
Hedgehog signaling pathway, Tumor, Regulatory mechanisms, Inhibitors, Therapeutic, Basal cell carcinoma.
Abstract: The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological processes
such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transformation,
and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive activation,
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 cancers,
including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast cancer.
Hence, the presence of mutations and excessive activation of the Hh pathway presents obstacles
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 focuses
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 elucidates
the obstacles encountered in targeting the Hh pathway for human cancer therapy and proposes
potential therapeutic approaches.
