Neutrophil extracellular traps in tumor progression: from mechanistic insights and regulatory factors to clinical detection and diagnosis.

Neutrophil extracellular traps (NETs), web-like DNA structures released by neutrophils, were initially recognized as key components of the anti-infective immune response but are now implicated in tumor progression. Tumor cells orchestrate the reprogramming of tumor-associated neutrophils (TANs) and trigger NET formation through paracrine signaling, thereby establishing a "tumor cell-TAN-NETs" positive feedback loop. This axis serves not only as a key hub for awakening dormant tumor foci and mediating immune evasion, but also as a core mechanism driving distant metastasis and dictating poor clinical prognosis. Notably, targeted disruption of this axis effectively reverses tumor therapy resistance and significantly sensitizes tumors to radiotherapy, chemotherapy, and immune checkpoint blockade, establishing NETs as novel therapeutic targets poised to overcome the current bottlenecks in cancer treatment. Nevertheless, limitations in detection technologies, prognostic modeling challenges, tumor heterogeneity, and inconsistent research findings constrain clinical translation. Future studies should prioritize optimizing detection methods, conducting rigorous clinical validation, and identifying specific therapeutic targets to accelerate the translational progress of NETs from basic research to clinical practice. This review synthesizes current knowledge on the biological mechanisms, regulatory pathways, and detection approaches of NETs, providing a theoretical basis for their clinical application in precision oncology.