Table 1.

Therapeutic strategies against pre-metastatic niche in clinic

Therapeutic Agent	Description	Phase	Cancer Type	Outcomes	Clinical Trials	References
Cilengitide	Integrins (αvβ3 and αvβ5) inhibitor	3	Glioblastoma	The addition of cilengitide to temozolomide chemoradiotherapy did not improve overall survival or progression-free survival	NCT00689221	[250]
Propagermanium	CCR2 inhibitor	1	Breast cancer	Propagermanium proved to be safe as an anti-metastatic drug	UMIN000022494	[251]
5-azacytidine and entinostat	DNA methyltransferase and histone deacetylase inhibitors	1/2	Lung cancer	One complete response and one partial response were observed	NCT00387465	[252]
		2	Breast cancer	One partial response was observed	NCT01349959	[253]
		2	Colorectal cancer	Combination epigenetic therapy proved to be well tolerated but without significant clinical activity	Unknown	[254]
		2	Lung cancer	Under evaluation	NCT01928576	N/A
Plerixafor	CXCR4 inhibitor	2	Pancreatic cancer	Under evaluation	NCT04177810	N/A
Denosumab	Anti-RANKL	3	Breast cancer	Denosumab did not improve bone metastasis-free survival	NCT01077154	[255]
		3	Breast cancer	Denosumab reduced the risk of clinical fractures and improved disease-free survival	NCT00556374	[256]
		3	Prostate cancer	Denosumab delayed initial bone metastases	NCT00286091	[257]
Siltuximab	Anti-IL-6	1/2	Solid tumours	Siltuximab proved to be well tolerated but without clinical activity	Unknown	[258]
Simtuzumab	LOXL2 antibody	2	Colorectal cancer	The addition of simtuzumab to FOLFIRI did not improve progression-free survival, overall survival or objective response rate	NCT01479465	[259]
		2	Pancreatic cancer	The addition of simtuzumab to gemcitabine did not improve progression-free survival, overall survival or objective response rate	NCT01472198	[260]
Andecaliximab	Anti-MMP9	3	Gastric cancer	The addition of andecaliximab to mFOLFOX6 did not improve overall survival	NCT02545504	[261]
Maraviroc	CCR5 blocker	1	Colorectal cancer	Anti-tumoral effects were observed at the tissue level	NCT01736813	[262]
		1	Colorectal cancer	Under evaluation	NCT03274804	N/A
Galunisertib	TGF-β receptor inhibitor	1b/2	Pancreatic cancer	The addition of galunisertib to gemcitabine improved overall survival with minimal added toxicity	NCT01373164	[263]
		1b/2	Solid tumours	Under evaluation	NCT02423343	N/A
Canakinumab	IL-1β inhibitor	3	Lung cancer	Under evaluation	NCT03631199	N/A

N/A Not applicable, RANKL Receptor activator of NF-κB ligand, LOXL Lysyl oxidase-like, MMP Matrix metalloproteinases, TGF-β Transforming growth factor-β