Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

Table 1

Selected clinical trials targeting altered signaling and tumor environment in OS.

Target	Drug	Type of drug	Clinical trial reference number (NCT number)
Cell membrane receptors
ERBB2	Trastuzumab	Monoclonal antibody	NCT00023998
IGF1R	Cixutumumab	Monoclonal antibody	NCT01016015/NCT00831844/NCT01614795/NCT00720174
	RG1507	Monoclonal antibody	NCT00642941
EGFR	ZD1839	Inhibitor	NCT00132158
PDGFR	Erlotinib	Inhibitor	NCT00077454
	Imatinib	Inhibitor	NCT00031915/NCT00030667
PRGFR/VEGFR	Sorafenib	Inhibitor	NCT01804374/NCT00889057/NCT00880542/NCT00330421/; NCT01518413
VEGFR	Pazopanib	Inhibitor	NCT01759303/NCT02357810/NCT01130623/NCT02180867/; NCT01532687/NCT01956669
	Bevacizumab	Monoclonal antibody	NCT00667342
	Endostar (rh-endostatin)	Inhibitor	NCT01002092
Intracellular signaling
mTOR	Everolimus	Inhibitor	NCT01216826
	Ridaforolimus	Inhibitor	NCT00093080/NCT00538239
WNT/β-catenin	Curcumin	Inhibitor	NCT00689195
Niche cells and their signaling
Osteoclasts	Zoledronic acid	Bisphosphonate	NCT00691236
	Pamidronate	Bisphosphonate	NCT00586846
RANKL	Denosumab	Monoclonal antibody	NCT02470091
Immune system	T cells expressing GD2	Cells	NCT02107963
	GD2Bi-armed T cells	Cells	NCT02173093
	Anti-GD2	Monoclonal antibody	NCT00743496/NCT02502786
	Stem and natural killer cells	Cells	NCT02409576/NCT01807468
	Mifamurtide	Monocyte/macrophage activator glycopeptide	NCT02441309/NCT00631631

Source: https://clinicaltrials.gov/. Osteosarcoma clinical trials: total: 363, open: 122.
ERBB2: Erb-B2 receptor tyrosine kinase 2; IGF1R: insulin-like growth factor 1 receptor; EGFR: epidermal growth factor receptor; PDGFR: platelet-derived growth factor receptor; VEGFR: vascular endothelial growth factor receptor; mTOR: mechanistic target of rapamycin; WNT: wingless-type MMTV integration site family; RANKL: receptor activator of nuclear factor kappa-B ligand.