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

## TL;DR

This review explains how neutrophil extracellular traps (NETs) contribute to cancer metastasis and explores potential therapies targeting them.

## Contribution

The paper provides a comprehensive overview of NETs' roles in metastasis and highlights novel therapeutic strategies.

## Key findings

- NETs contribute to multiple stages of metastasis, including tumor cell survival and colonization.
- Psychological stress and tumor-secreted cytokines are key drivers of NET formation.
- Targeting NETs may offer new treatment options for metastatic cancer.

## Abstract

Metastasis is the leading cause of cancer-related deaths, highlighting the need to understand its mechanisms. Neutrophil extracellular traps (NETs) play a crucial role in tumor progression and metastasis. This review discusses the primary stimuli and signaling pathways driving NET formation, including factors like psychological stress, tumor-secreted cytokines, and treatment responses. NETs contribute to various stages of metastasis, including angiogenesis, tumor cell intravasation and extravasation, circulating tumor cell survival, metastatic colonization, and dormant tumor cell reactivation. They also help establish an immunosuppressive microenvironment. Finally, emerging strategies targeting NETs are explored for their potential in metastatic cancer treatment.

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.