{"doi":"10.20944/preprints202504.0682.v1","title":"A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease","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 the complexity of NETs regarding its 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>","journal":null,"year":null,"id":635198,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1647881,"name":"Kim Maree O’Sullivan","orcid":"0000-0002-3098-7948","position":1,"is_corresponding":false},{"id":1647879,"name":"Andre Espiritu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease","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 the complexity of NETs regarding its 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>","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W4409287770","authors":[],"funders":[{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"2001325","title":"Unravelling NET confusion in Vasculitis"}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":4}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.preprints.org/frontend/manuscript/60133b23925592c1afc2d01688f7ded8/download_pub","host_type":"repository"},{"url":"https://www.preprints.org/frontend/manuscript/60133b23925592c1afc2d01688f7ded8/download_pub","host_type":"repository"},{"url":"https://doi.org/10.20944/preprints202504.0682.v1","host_type":"repository"},{"url":"https://doi.org/10.3390/ijms26104773","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/40429915","host_type":""},{"url":"http://dx.doi.org/10.3390/ijms26104773","host_type":""}],"fields_of_study":["Phosphodiesterase function and regulation","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Disease","Computer science","Political science","Medicine","Internal medicine","Inflammation","Neutrophils","Neoplasms","Humans","Animals","Medicine and Pharmacology","Review","Extracellular Traps","Autoimmune Diseases"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:45:52.330928Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}