Table 5.

Biologic agents with potential synergy against Ewing's sarcoma (EWS).

Drug	Comments	Reference
Bisphosphonates	Zoledronate, a potent inhibitor of EWS cell growth in vitro	[51]
Metformin	Metformin inhibits both the mTORC1 pathwayand the IGF1R/IRS-1 pathway and at the same time downregulates the phosphorylation of Akt onserine 473	[52, 53]
Anti-angiogenic agents (bevacizumab)	Preclinical studies: VEGF inhibition suppresses EWS growth. Three of five EWS patients had stable disease for >4 months in a phase I study of bevacizumab	[54, 55]

mTOR: mammalian target of rapamycin; IGF1R: insulin-like growth factor 1 receptor; IRS-1: insulin receptor substrates 1; VEGF: vascular endothelial growth factor.