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J Hematol Oncol. 2019 Jul 5;12(1):71. doi: 10.1186/s13045-019-0754-1.

Targeting mTOR for cancer therapy.

Author information

1
State Key Laboratory of Biotherapy, Laboratory of Stem Cell Biology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.
2
Laboratory of Oncogene, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
3
School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
4
Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
5
Laboratory of Oncogene, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. jyangfu@scu.edu.cn.

Abstract

Mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. mTOR is usually assembled into several complexes such as mTOR complex 1/2 (mTORC1/2). In cooperation with raptor, rictor, LST8, and mSin1, key components in mTORC1 or mTORC2, mTOR catalyzes the phosphorylation of multiple targets such as ribosomal protein S6 kinase β-1 (S6K1), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, protein kinase C (PKC), and type-I insulin-like growth factor receptor (IGF-IR), thereby regulating protein synthesis, nutrients metabolism, growth factor signaling, cell growth, and migration. Activation of mTOR promotes tumor growth and metastasis. Many mTOR inhibitors have been developed to treat cancer. While some of the mTOR inhibitors have been approved to treat human cancer, more mTOR inhibitors are being evaluated in clinical trials. Here, we update recent advances in exploring mTOR signaling and the development of mTOR inhibitors for cancer therapy. In addition, we discuss the mechanisms underlying the resistance to mTOR inhibitors in cancer cells.

KEYWORDS:

Cancer; Drug resistance; Oncogene; Targeted therapy; mTOR

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