The Hedgehog/Glioma-associated oncogene homolog (HH/GLI) signaling pathway regulates self-renewal of rare and highly malignant cancer stem cells, which have been shown to account for the initiation and maintenance of tumor growth as well as for drug resistance, metastatic spread and relapse. As an important component of the Hh signaling pathway, glioma-associated oncogene (GLI) acts as a key signal transmission hub for various signaling pathways in many tumors. Here, we review direct and indirect inhibitors of GLI; summarize the abundant active structurally diverse natural GLI inhibitors; and discuss how to better develop and utilize GLI inhibitors to solve the problem of drug resistance in tumors of interest. In summary, GLI inhibitors will be promising candidates for various cancer treatments.
Keywords: Crosstalk in GLI pathways; GLI code; GLI inhibitors; Hedgehog pathway; Natural products; Signal transmission hub.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.