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Int J Biol Sci 2023; 19(16):5089-5103. doi:10.7150/ijbs.87334 This issue Cite

Review

The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics

Congkuan Song1,#, Jinjin Zhang2,#, Chenzhen Xu1,#, Minglang Gao1, Ning Li1,✉, Qing Geng1,✉

1. Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
2. Department of Emergency, Taihe Hospital, Shiyan, China.
# These authors contributed equally to this work.

✉ Corresponding authors: Qing Geng, MD, Department of Thoracic Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan 430060, China. Telephone number: +86-27-8804-1919; Fax number: +86-27-8807-2292; E-mail address: More

Citation:
Song C, Zhang J, Xu C, Gao M, Li N, Geng Q. The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics. Int J Biol Sci 2023; 19(16):5089-5103. doi:10.7150/ijbs.87334. https://www.ijbs.com/v19p5089.htm
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Abstract

Graphic abstract

As a multi-substrate transmembrane protease, γ-secretase exists widely in various cells. It controls multiple important cellular activities through substrate cleavage. γ-secretase inhibitors (GSIs) play a role in cancer inhibition by blocking Notch cleavage, and are considered as potential therapeutic strategies for cancer. Currently, GSIs have encouraging performance in preclinical models, yet this success does not translate well in clinical trials. In recent years, a number of breakthrough discoveries have shown us the promise of targeting γ-secretase for the treatment of cancer. Here, we integrate a large amount of data from γ-secretase and its inhibitors and cancer in nearly 30 years, comb and discuss the close connection between γ-secretase and cancer, as well as the potential and problems of current GSIs in cancer treatment. We analyze the possible reasons for the failure performance of current GSIs in clinical trials, and make recommendations for future research areas.

Keywords: γ-secretase, γ-secretase inhibitors (GSIs), cancer

Citation styles

APA
Song, C., Zhang, J., Xu, C., Gao, M., Li, N., Geng, Q. (2023). The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics. International Journal of Biological Sciences, 19(16), 5089-5103. https://doi.org/10.7150/ijbs.87334.

ACS
Song, C.; Zhang, J.; Xu, C.; Gao, M.; Li, N.; Geng, Q. The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics. Int. J. Biol. Sci. 2023, 19 (16), 5089-5103. DOI: 10.7150/ijbs.87334.

NLM
Song C, Zhang J, Xu C, Gao M, Li N, Geng Q. The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics. Int J Biol Sci 2023; 19(16):5089-5103. doi:10.7150/ijbs.87334. https://www.ijbs.com/v19p5089.htm

CSE
Song C, Zhang J, Xu C, Gao M, Li N, Geng Q. 2023. The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics. Int J Biol Sci. 19(16):5089-5103.

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