Table 1. Research status of mTOR in the context of OS.

Publication	Name	Main Findings	Ref
2005,2009 2013,2015	Rapamycin	Rapamycin can inhibit OS cell proliferation, metastasis, and induce autophagy.	[22][33][34] [44][61]
2010	Everolimus	Combination with ZOL(zoledronate, an anti-osteoporotic drug) augments the inhibition of Everolimus in cell proliferation.	[65]
2011	Oleanolic acid (OA)	OA exhibits potent anti-tumor activity against osteosarcoma cells	[23]
2011	Cucurbitacin B	Cucurbitacin B alone or in combination with methotrexate(MTX) exerts anti-tumor effects on human OS	[66]
2012	Ridaforolimus	In Phase II study, ridaforolimus shows promising anti-proliferative activity against OS	[62]
2013	Everolimus	Sorafenib in combined with everolimus contributes to an increasing antitumor activity	[67]
2014	NVP-BEZ235	NVP-BEZ235, a dual PI3K/mTOR inhibitor, shows promising antitumor activity in OS.	[72]
2014	Temsirolimus	Temsirolimus combined with cisplatin or bevacizumab exerts synergistic effects for treatment of OS.	[68]
2014	PP242	Inhibition of mTORC2 effectively promotes cisplatin-induced apoptosis	[60]
2014	Temsirolimus, LY294.002 and PP242	mTOR inhibitors can blunt the p53 response to nucleolar stress in OS.	[79]
2015	Rapamycin	JQ1 and rapamycin synergistically inhibite the growthl of OS cells in vitro and in vivo.	[69]
2015	Temsirolimus	In this phase II trial the combination of cixutumumab and temsirolimus does not show objective result.	[78]
2015	Everolimus	The combination of sorafenib and everolimusdoes not attain the prespecified target of 6 month PFS in a non-randomised phase 2 clinical trial	[70]
2015	MLN0128	MLN0128 exerts anti-tumor activity in in vitro and in vivo model of OS.	[63]
2015	NVP-BEZ235	NVP-BEZ235 shows promising anti-tumor activity, which is enhanced by MEK/Erk inhibitors	[73]
2015	INK-128	INK-128 exibit potent anti-OS activity in vitro and in vivo.	[64]
2016	Rapamycin	The combination of rapamycin and an autophagy inhibitor exerts synergistic effects for treatment of OS byeffectively promoting the apoptotic pathway.	[71]