Neutrophil Extracellular Traps in Cancer Metastasis: From Mechanistic Understanding to Targeted Therapy

Metastasis is the leading cause of cancer-related death, underscoring the need to elucidate the key mechanisms behind this process. Neutrophil extracellular traps (NETs) have emerged as critical regulators of tumor progression and metastasis. This review summarizes the primary stimuli and signaling pathways that govern NET formation and outlines the mechanistic roles of NET components in tumor growth and metastatic spread. We focus on environmental and tumor microenvironment-derived factors, including psychological stress, tumor-secreted cytokines, and treatment-related responses, that drive NET formation. The involvement of NETs in multiple stages of the metastatic cascade is discussed, including angiogenesis, tumor cell intravasation and extravasation, circulating tumor cell survival, metastatic colonization, and the reactivation of dormant tumor cells. Additionally, we examine how NETs contribute to the establishment of an immunosuppressive microenvironment. Finally, emerging therapeutic strategies targeting NETs are briefly reviewed, highlighting their potential relevance in metastatic cancer treatment.