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Review
. 2016 Aug 2;7(31):50805-50813.
doi: 10.18632/oncotarget.9305.

mTOR: An attractive therapeutic target for osteosarcoma?

Liu Ding  1 , Liu Congwei  1 , Qing Bei  2 , Yang Tao  3 , Wang Ruiguo  4 , Yu Heze  4 , Dou Bo  4 , Li Zhihong  1
Affiliations
Review

mTOR: An attractive therapeutic target for osteosarcoma?

Liu Ding et al. Oncotarget. .

Abstract

Osteosarcoma (OS) is a common primary malignant bone tumor with high morbidity and mortality in children and young adults. How to improve poor prognosis of OS due to resistance to chemotherapy remains a challenge. Recently, growing findings show activation of mammalian target of rapamycin (mTOR), is associated with OS cell growth, proliferation, metastasis. Targeting mTOR may be a promising therapeutic approach for treating OS. This review summarizes the roles of mTOR pathway in OS and present research status of mTOR inhibitors in the context of OS. In addition, we have attempted to discuss how to design a better treatment project for OS by combining mTOR inhibitor with other drugs.

Keywords: apoptosis; autophagy; mTOR; osteosarcoma; target.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Overview of mTOR signaling pathway
Activation of PI3K/AKT pathway can stimulate mTORC1, meanwhile mTORC1are negatively regulated by AMPK. Activation of mTORC1 upregulates CDK and phosphorylates S6K1 and 4EBP1, modulating cellular growth, autophagy, and apoptosis process. Additionally, PI3K is also the upstream controller of mTORC2, activation of which phosphorylates AKT, forming a positive feedback to enhance the signal. Moreover, activation of mTOR2 is involved in insulin sensitivity and cytoskeletal reorganization.
Figure 2
Figure 2. The roles of mTOR pathway in OS cell
See this image and copyright information in PMC

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