Neutrophil extracellular traps facilitate cancer metastasis: cellular mechanisms and therapeutic strategies

Background The formation of neutrophil extracellular traps (NETs) was initially discovered as a novel immune response against pathogens. Recent studies have also suggested that NETs play an important role in tumor progression. This review summarizes the cellular mechanisms by which NETs promote distant metastasis and discusses the possible clinical applications targeting NETs. Method The relevant literature from PubMed and Google Scholar (2001-2021) have been reviewed for this article. Results The presence of NETs has been detected in various primary tumors and metastatic sites. NET-associated interactions have been observed throughout the different stages of metastasis, including initial tumor cell detachment, intravasation and extravasation, the survival of circulating tumor cells, the settlement and the growth of metastatic tumor cells. Several in vitro and in vivo studies proved that inhibiting NET formation resulted in anti-cancer effects. The biosafety and efficacy of some NET inhibitors have also been demonstrated in early phase clinical trials. Conclusions Considering the role of NETs in tumor progression, NETs could be a promising diagnostic and therapeutic target for cancer management. However, current evidence is mostly derived from experimental models and as such more clinical studies are still needed to verify the clinical significance of NETs in oncological settings.

Automated summary

This review summarizes the cellular mechanisms by which neutrophil extracellular traps (NETs) promote tumor progression and discusses the potential clinical applications of targeting NETs. Various primary tumors and metastatic sites have been found to have presence of NETs. Inhibition of NET formation has shown anti-cancer effects in both in vitro and in vivo studies. The biosafety and efficacy of NET inhibitors have also been demonstrated in early phase clinical trials. However, more clinical studies are needed to validate the clinical significance of NETs in oncology.