# The Molecular Network of Neutrophil Extracellular Traps in Hepatocellular Carcinoma: Biogenesis, Function, and Therapeutic Implications

## TL;DR

This review explores how neutrophil extracellular traps (NETs) contribute to the progression and treatment resistance of hepatocellular carcinoma (HCC), offering insights into new therapeutic strategies.

## Contribution

The paper provides a systematic analysis of molecular networks linking NETs to HCC, highlighting their roles in tumor progression and therapeutic implications.

## Key findings

- NETs promote HCC progression by trapping tumor cells and remodeling the extracellular matrix.
- NETs contribute to immune evasion and therapy resistance in HCC.
- NETs show potential as diagnostic biomarkers and therapeutic targets in HCC.

## Abstract

Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related death worldwide. Its high aggressiveness and resistance to therapy arise, in large part, from an immunosuppressive tumor microenvironment (TME). Neutrophil extracellular traps (NETs) are web-like assemblies of chromatin and granular proteins released during NETosis, and they have emerged as major inflammatory drivers within the HCC TME. NETs actively promote tumor progression by physically trapping circulating tumor cells, remodeling the extracellular matrix, stimulating angiogenesis, and facilitating immune evasion. In this review, we systematically dissect the molecular networks that link NETs to HCC. We summarize the signaling pathways that regulate NETs formation, detail the multifaceted roles of NETs in hepatocarcinogenesis, metastasis, and therapy resistance, and assess the translational potential of NETs as diagnostic biomarkers and therapeutic targets. Together, these analyses offer theoretical guidance for developing the next generation of precision-medicine strategies for HCC.