Table 2.

Potential NET-Based Therapies.

Target	Drug	Intended Mechanism of Action	Potential Impact on Tumour Metastasis
Histones	STC3141 [142], Unfractionated Heparin [143]	Small/large polyanions that interact electrostatically with histones, thereby neutralising their pathological effects	Inhibition of histone-dependent pro-tumorigenic pathways such as TLR4/histone-dependent immunosuppression in TME, histone-dependent endothelial or platelet activation/thrombosis that help confer tumour survival and metastatic ability
Neutrophil Elastase (NE)	Sivelestat [144]	Competitive inhibitor of the NET-expressed serine protease	NE is integral to NETosis and has been shown to attenuate hepatic metastasis in a preclinical model of colorectal cancer
CXCR1/2:IL-8	SX-682/Avarixin [145,146], NCT03161431, NCT03473925	Neutrophil chemotaxis and NETosis inhibition	Suppressing myeloid cell recruitment
PKC	Metformin [147,148,149,150,151]	Attenuates NETosis by inhibiting PKC	Studies show metformin-mediated reduction in circulating NET markers and abrogation of NET promoted carcinogenesis in preclinical models
COX-1	Aspirin [152,153,154]	Inhibition of platelet-dependent expression of neutrophil chemokines CXCL4 and CCL5	Studies have demonstrated the anti-metastatic effects of ameliorating NET production via COX-1 inhibition.
DNA	Dornase alfa [155,156]	Cleaves extracellular DNA	rhDNase 1 has been shown to attenuate metastasis in preclinical models of lung, breast, and pancreatic cancer