Neutrophils and Neutrophil Extracellular Traps in Cancer and Cardio-Oncology: Molecular Mechanisms, Therapeutic Targeting, and Clinical Perspectives

Abstract

Neutrophils are key regulators of innate immunity and, in addition to their antimicrobial function, contribute to the progression of tumors by forming extracellular traps (NETs). Within the tumor microenvironment, the NETs interact with tumor cells, immune cells, fibroblasts and endothelial cells to promote tumor growth, angiogenesis, immune suppression, metastasis and resistance to treatment. This review critically examines the molecular mechanisms underlying intercellular communication mediated by NETs in cancer and examines their impact on disease progression and response to treatment. In addition, we assess current therapeutic approaches focused on NETs, discuss the available clinical evidence and highlight the main limitations, including safety concerns, validation of biomarkers and translational challenges. We also outline unresolved issues and future research priorities, emphasizing the need for more mechanistic and clinical studies. In addition to oncology, NETs can also play a role in cardio-oncology by linking cancer-related inflammation to thrombosis and cardiotoxicity. Overall, this review provides an integrated framework for understanding the biological and clinical relevance of NETs and supports their potential as a therapeutic target and biomarker in precision medicine.