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Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy

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Abstract

Autophagy is a highly conserved catabolic process and participates in a variety of cellular biological activities. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, as a critical regulator of autophagy, is involved in the initiation and promotion of a series of pathological disorders including various tumors. Autophagy also participates in regulating the balance between the tumor and the tumor microenvironment. Natural products have been considered a treasure of new drug discoveries and are of great value to medicine. Mounting evidence has suggested that numerous natural products are targeting PI3K/AKT/mTOR-mediated autophagy, thereby suppressing tumor growth. Furthermore, autophagy plays a “double-edged sword” role in different tumors. Targeting PI3K/AKT/mTOR-mediated autophagy is an important therapeutic strategy for a variety of tumors, and plays important roles in enhancing the chemosensitivity of tumor cells and avoiding drug resistance. Therefore, we summarized the roles of PI3K/AKT/mTOR-mediated autophagy in tumorigenesis, progression, and drug resistance of tumors, which may be utilized to design preferably therapeutic strategies for various tumors.

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Funding

This work was funded by the National Natural Science Foundation of China (No. 81870105 and 81770107), the National Key Research and Development Program of China (2018YFA0107800), and Key Project of Science and Technology of Hunan Provincial Health Commission (No.20201921) .

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  1. Zhenru Xu and Xu Han contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China

    Zhenru Xu, Daming Ou, Ting Liu & Ji Zhang

  2. Molecular Biology Research Center & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China

    Xu Han & Jing Liu

  3. University of South China, Hengyang, Hunan, China

    Zunxiong Li

  4. Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China

    Guanmin Jiang

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  1. Zhenru Xu
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  2. Xu Han
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  4. Ting Liu
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  5. Zunxiong Li
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Contributions

Z.R.X. wrote the manuscript, summarized tables; X.H. reviewed the manuscript and revised the manuscript; T.L., D.M.O., and Z.X.L. reviewed the manuscript and prepared figures; G.M.J. helped manuscript review; J.L. and J.Z. conceived the projects and revised the manuscript. All authors accepted the final version of the manuscript.

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Correspondence to Jing Liu or Ji Zhang.

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Xu, Z., Han, X., Ou, D. et al. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy. Appl Microbiol Biotechnol 104, 575–587 (2020). https://doi.org/10.1007/s00253-019-10257-8

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