{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:08:39Z","timestamp":1794020919740,"version":"4.8.0"},"reference-count":160,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Research Council Ideas","award":["2YID 200132S 20020579"],"award-info":[{"award-number":["2YID 200132S 20020579"]}]},{"name":"Australian Government Research Training Program (RTP) Scholarship","award":["2YID 200132S 20020579"],"award-info":[{"award-number":["2YID 200132S 20020579"]}]},{"name":"NHMRC Stipend Scholarship","award":["2YID 200132S 20020579"],"award-info":[{"award-number":["2YID 200132S 20020579"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophil extracellular traps (NETs) play a crucial role in the pathophysiology of many debilitating conditions, including autoimmune diseases, inflammatory diseases, and cancer. As a result, NET-targeted therapies have been investigated in search of effective treatment strategies. Despite promising preclinical findings, clinical translation of NET inhibitors has had limited success. These preclinical studies have faced limitations such as mouse models that inaccurately reflect human disease dynamics, as well as by the complexity of NETs\u2014including their diverse morphology and convoluted pathways to formation relative to pathology. The NET inhibitors themselves have several limitations, including off-target effects and bioavailability issues. The challenges facing NET-targeted therapies reported here may explain what is required to go from bench to bedside successfully.<\/jats:p>","DOI":"10.3390\/ijms26104773","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"4773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Andre","family":"Espiritu","sequence":"first","affiliation":[{"name":"Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-7948","authenticated-orcid":false,"given":"Kim Maree","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1182\/blood.V100.3.854","article-title":"Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation","volume":"100","author":"Basu","year":"2002","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/ni.2109","article-title":"Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils","volume":"12","author":"Galli","year":"2011","journal-title":"Nat. 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