Table 2. Examples of drugs that target the tyrosine kinase receptors that have been tested in GBM.

Target	Drug	Preclinical activity	Clinical trials	References
PI3K	PX-866	In vitro cell cycle arrest and in vivo tumour growth inhibition	Phase II for recurrent GBM	108,109
mTOR	Temsirolimus (CCI-779)	In vivo activity on cells implanted in nude mice	Phase II for recurrent GBM	112
	Sirolimus (Rapamycin)	—	Phase II for recurrent GBM in combination with Erlotinib	113
	Everolimus (RAD001)	—	Phase II for recurrent GBM in combination with Sirolimus, Phase II for newly diagnosed GBM, Phase I/II trial with Sorafenib for recurrent GBM currently recruiting NCT01434602	113,114
	AZD2014 (Vistusertib)	Radiosensitisation of GBM stem-like cells in vitro	Phase I/II for previously treated GBM currently recruiting NCT02619864	115
	CC-223 (TORKi)	In vivo Xenograft activity	—	116
	Palomid 529	In vivo orthotopic xenograft GBM activity	—	117
PI3K/mTOR	XL765	In vitro and In vivo activity	—	110
	GDC-0084	In vitro and In vivo activity observed	Phase I trial for recurrent GBM has been completed NCT01547546	111
PKCβ/PI3K	Enzastaurin	In vitro and in vivo activity observed using GBM cell lines and murine xenografts	Phase III for recurrent GBM	126
Ras	Zoledronic acid	In vitro and in vivo activity	—	120,121
RAF	Sorafenib	—	Phase II trial in combination with Erlotinib for recurrent GBM, Phase I/II trial with Everolimus for recurrent GBM currently recruiting NCT01434602	122
PKC	Tamoxifen	—	Phase II for newly diagnosed GBM	123–125
p53	SGT-53	In vitro chemosensitisation of GBM cell lines to TMZ and In vivo activity when combined with TMZ	Phase II study for recurrent GBM currently recruiting NCT02340156	131
	Ad-p53	—	Phase I trial for recurrent GBM	132
Cdk4/6	PD0332991 (Palbociclib)	In vitro GBM cell cycle arrest and In vivo intracranial xenograft growth inhibition	Phase I trial recruiting for young patients with nervous system tumours NCT02255461	136