Neutrophil extracellular traps (NETosis) in gynecologic cancers: from pathogenesis to therapeutic opportunities: a narrative review

Clin Transl Oncol. 2026 Jan 23. doi: 10.1007/s12094-025-04149-9. Online ahead of print.

Abstract

Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin coated with antimicrobial proteins, released by activated neutrophils as part of innate immunity. Evidence links NETs to cancer-related processes like tumor growth, metastasis, tumor microenvironment. This narrative review synthesizes current evidence on roles of NETs in gynecological cancers. Comprehensive narrative review was conducted to summarize evidence on NETs in gynecological cancers. Literature searches were performed in PubMed, Scopus, Web of Science, Google Scholar using keywords like "neutrophil extracellular traps," "NETs," "ovarian cancer," "endometrial cancer," "cervical cancer," "tumor microenvironment," "metastasis," "biomarkers." Articles published up to August 2025 in English were included. Studies focusing exclusively on other cancers or non-gynecological inflammatory conditions were excluded. Findings were synthesized, highlighting NET formation, functional roles, diagnostic, and therapeutic potentials in gynecological cancers. NETs exhibit a dual role in gynecological cancers, contributing to tumor progression and therapy resistance while also presenting valuable diagnostic and therapeutic opportunities. Their components-NE, MPO, CitH3, cfDNA, and ctDNA are emerging as promising biomarkers for disease monitoring and prognosis. Targeting NETs through DNase therapy, PAD4 inhibition, ROS modulation, or immune regulation holds potential to enhance treatment efficacy and support personalized management of gynecological cancers.

Keywords: Chromatin; Gynecological cancers; Neutrophil extracellular traps; Reactive oxygen species; Tumor microenvironment.

Publication types

  • Review