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Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy

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Summary

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.

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Acknowledgements

The authors sincerely thank all the participants for their involvement in this article and AJE for editing the manuscript.

Funding

This research was supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LGF20H300001) and the National Natural Science Foundation of China (Grant No. 81803404).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, China

    Meng Zhang, Lijuan Gao, Yiping Ye & Xiaoyu Li

  2. Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou, Zhejiang, China

    Meng Zhang, Lijuan Gao, Yiping Ye & Xiaoyu Li

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  1. Meng Zhang
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  2. Lijuan Gao
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MZ drafted the first version of the manuscript; XL, LG, YY and MZ revised and edited the manuscript; MZ collected and organized the references; and XL approved the final version of the paper.

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Correspondence to Xiaoyu Li.

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Zhang, M., Gao, L., Ye, Y. et al. Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy. Invest New Drugs 40, 370–388 (2022). https://doi.org/10.1007/s10637-021-01187-2

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