NETs in the tumor microenvironment: mechanisms, biomarkers, and therapy

This Research Topic is the second volume of the “The Role of Neutrophil Extra Cellular Traps (NETs) Formation in Tumor Microenvironment- from Basic Research to Clinical Applications”. Please see Volume I here.Neutrophil extracellular traps (NETs) are intricate structures released by neutrophils to ensnare pathogens. While crucial for host defence, NETs have been implicated as key players in tumor progression. These extracellular webs composed of DNA, histones, and cytotoxic proteins, infiltrate the tumor microenvironment (TME) of various cancers, including pancreatic, colorectal, and triple-negative breast cancers. Moreover, NETs are increasingly recognized for their role in pediatric malignancies like Ewing sarcoma and osteosarcoma. By promoting metastasis, shielding cancer stem cells, and conferring treatment resistance, NETs create a complex and challenging landscape for cancer therapy. Deciphering the mechanisms underlying NET-mediated tumor progression is essential for developing innovative treatments that can harness their potential as therapeutic targets.NETs have shown significant promise as therapeutic targets in preclinical cancer models. However, translating these findings into effective clinical treatments remains a critical challenge. Although numerous in vitro and animal studies have demonstrated the potential of combining DNase, an enzyme that dissolves NETs, with chemotherapy or immunotherapy to hinder tumor progression and metastasis, this approach has yet to be tested in human subjects. The goal of this research is to identify specific cancer types where NETs play a significant role in disease progression, metastasis, and treatment resistance. By targeting these cancers, we can explore the clinical potential of combining anti-NET therapies, such as DNase or NET formation inhibitors, with existing treatments. This approach holds promise for enhancing treatment efficacy, reducing metastasis, and overcoming resistance to standard therapies. Ultimately, this research aims to pave the way for the development of novel therapeutic strategies that could be integrated into clinical practice, offering new hope for patients with NETs-associated cancers.This Research Topic focuses on advancing our understanding of the role of NETs in cancer progression and developing effective NETs-targeted therapies. We welcome the submission of Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to the following themes:• Therapeutic targeting of NETs: Developing novel strategies to modulate NETs formation, stability, or function for cancer treatment.• Combination therapies: Exploring the synergistic effects of anti-NETs therapies with conventional cancer treatments.• NETs in cancer biology: Delineating the mechanisms by which NETs contribute to tumor initiation, growth, metastasis, and therapeutic resistance.• NETs as prognostic and predictive biomarkers: Identifying NET-based biomarkers for cancer diagnosis, staging, and treatment response.• Clinical translation: Bridging the gap between basic research and clinical application of NET-targeted therapies.• Overcoming challenges: Addressing obstacles in NET-targeted drug development and clinical trials.The next critical step in advancing our understanding of NETs in cancer involves translating basic research findings into clinical applications. Although numerous in vitro and animal studies have demonstrated the potential of combining DNase, an enzyme that dissolves NETs, with chemotherapy or immunotherapy to hinder tumor progression and metastasis, this approach has yet to be tested in human subjects.• Original research to identify specific cancer types where NETs play a significant role in disease progression, metastasis, and treatment resistance.• Papers regarding targeting these cancers and explore the clinical potential of combining anti-NET therapies, such as DNase or NET formation inhibitors, with existing treatments.• New approaches that will hold promise for enhancing treatment efficacy, reducing metastasis, and overcoming resistance to standard therapies.• Research that will pave the way for the development of novel therapeutic strategies that could be integrated into clinical practice, offering new hope for patients with NETs-associated cancers.Please note that Dr. Alexey Stepanov serves as a Scientific Steering Committee member and consultant for Xenetic Biosciences, a private biotechnology company active in a field relevant to this Research Topic. All remainder Topic Editors declare no conflicts of interest. Topic editors: Ronit Elhasid, Alexey Stepanov, Rachel Shukrun Source: https://www.frontiersin.org/research-topics/80452/nets-in-the-tumor-microenvironment-mechanisms-biomarkers-and-therapy