{"entity":{"id":"idea-bio2-net-blockade-perioperative","kind":"idea","name":"Break the neutrophil DNA nets that catch tumour cells after surgery","aka":[],"tldr":"Surgery makes some immune cells throw out sticky DNA webs that trap travelling cancer cells and help them settle. Dissolving those webs during the operation might prevent some relapses.","summary":"Neutrophil extracellular traps capture circulating tumour cells and promote liver and lung seeding in multiple mouse models, and trap markers rise sharply after large cancer operations. DNase I is an approved inhaled drug and PAD4 inhibitors are in development, so a perioperative net-dissolving window trial is quick and cheap to run.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal","pancreatic"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":["erik-sahai"],"bottlenecks":["b-metastasis-biology","b-dormancy-mrd"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Perioperative net degradation with DNase or a PAD4 inhibitor reduces postoperative ctDNA positivity at four weeks by a third after colorectal or pancreatic resection, and lowers two-year distant relapse.","rationale":"The postoperative period is a brief, defined window of raised metastatic risk, and neutrophil traps are one of the few molecular explanations for it that already has drugs in hand and measurable pharmacodynamics.","test":"A 120-patient randomised window trial in colorectal liver resection or pancreatic resection with day-28 ctDNA as primary endpoint and trap markers such as citrullinated histone H3 as pharmacodynamic readouts.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio2-net-blockade-perioperative/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"person":[{"id":"erik-sahai","kind":"person","name":"Erik Sahai","route":"/people/erik-sahai/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"}],"paper":[{"id":"paper-dillekas-cancer-med","kind":"paper","name":"Are 90% of deaths from cancer caused by metastases?","route":"/key-papers/paper-dillekas-cancer-med/"}]}}