{"entity":{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","aka":[],"tldr":"After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them.","summary":"Disseminated tumour cells can persist for years in bone marrow, liver, lung or brain in a non-proliferative state, invisible to imaging and untouched by cytotoxic agents that require cell division. In oestrogen receptor-positive breast cancer, distant recurrence continues at a steady rate for at least twenty years after diagnosis; in colorectal, bladder and lung cancer, detectable circulating tumour DNA after curative surgery predicts relapse with high specificity months before scans. Detection is now possible, but the therapeutic side lags: there are few drugs designed to kill quiescent cells or to keep them asleep, no validated biomarkers of dormancy, and until recently no trials that acted on a molecular residual disease signal. The first ctDNA-guided adjuvant trials show that the signal can be used to de-escalate safely; whether escalation on a positive test improves survival is the open question.","asOf":"2026-09-08","links":[{"label":"Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"},{"label":"Pan et al., 20-year risks of breast-cancer recurrence (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1701830"},{"label":"Phan & Croucher, The dormant cancer cell life cycle (Nature Reviews Cancer 2020)","url":"https://doi.org/10.1038/s41568-020-0263-0"}],"tags":[],"related":["idea-late-recurrence-interception","idea-ctdna-guided-adjuvant-crc","idea-ctdna-guided-adjuvant-melanoma","idea-mrd-guided-stop-myeloma","idea-ctdna-escalation-tnbc","idea-bio2-dormancy-selective-screen","idea-bio2-autophagy-block-mrd","idea-bio2-pro-dormancy-therapy","idea-bio2-il1-awakening-blockade","idea-bio2-national-mrd-platform","idea-bio2-mrd-reference-standards","idea-bio2-mrd-triggered-neoantigen-vaccine","idea-bio2-nk-cells-for-mrd","idea-bio2-whole-genome-mrd-depth","idea-bio2-marrow-niche-on-chip","idea-bio2-localise-the-mrd","idea-bio2-circadian-mrd-sampling","idea-bio2-mrd-guided-endocrine-duration","idea-bio2-mrd-clinic-service","idea-bio2-survivor-plasma-biobank","idea-moon-engineered-immune-surveillance","idea-moon-mrd-weather-service","idea-moon-dormancy-eradication-programme"],"cancers":["breast-hr-positive","colorectal","urothelial","nsclc","multiple-myeloma","aml","all-leukemia"],"sections":[],"technologies":["mrd-testing","ngs-mrd-clonoseq","liquid-biopsy","flow-cytometry-mrd","ctdna-lymphoma-monitoring"],"targets":[],"drugs":["signatera"],"companies":["natera","foresight-diagnostics","adaptive-biotechnologies","guardant-health"],"institutions":[],"pathways":[],"terms":["mrd","ctdna","late-recurrence","mrd-negativity-myeloma","mrd-negative-cr","neoadjuvant-adjuvant"],"trials":["dynamic","circulate-japan","imvigor011","cambria","natalee"],"people":[],"bottlenecks":[],"keyPapers":["paper-phan-nat-rev-cancer","paper-pan-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"stage":"biology","severity":"critical","metrics":[{"label":"Risk of distant recurrence in years 5-20 for ER-positive breast cancer after 5 years of endocrine therapy, by original stage","value":"10% to 41%","source":"Pan et al., NEJM 2017","url":"https://doi.org/10.1056/NEJMoa1701830"},{"label":"Adjuvant chemotherapy use with ctDNA-guided vs standard management in stage II colon cancer (DYNAMIC), with non-inferior recurrence-free survival","value":"15% vs 28%","source":"Tie et al., NEJM 2022","url":"https://doi.org/10.1056/NEJMoa2200075"}],"causes":["Quiescent cells do not divide, so chemotherapy and many targeted agents have nothing to act on.","Dormant cells are rare and dispersed, below the resolution of any imaging modality.","The signals that hold cells dormant or awaken them (niche, immune surveillance, inflammation, surgery) are only partly characterised and have no drugs.","Adjuvant trials treat everyone because there has been no way to identify who still harbours disease.","Reimbursement and guidelines have been slow to adopt molecular residual disease assays outside haematology."],"currentEfforts":["Natera's Signatera and Foresight Diagnostics' PhasED-Seq are tumour-informed ctDNA assays used in interventional trials of MRD-guided therapy.","DYNAMIC and CIRCULATE-Japan (GALAXY/VEGA/ALTAIR) test ctDNA-guided escalation and de-escalation of adjuvant chemotherapy in colon cancer.","IMvigor011 randomises ctDNA-positive patients after cystectomy to atezolizumab or placebo, a phase 3 that acts only on a molecular signal.","The CAMBRIA trials in breast cancer test switching to an oral SERD in patients at risk of late recurrence.","clonoSEQ (Adaptive Biotechnologies) is FDA-cleared for MRD in myeloma and leukaemia, and MRD negativity has been accepted by the FDA as an endpoint for accelerated approval in myeloma.","Cancer Grand Challenges funds teams working specifically on the biology of tumour dormancy."],"successLooksLike":"A positive molecular residual disease test after curative therapy triggers a treatment that is proven to prevent relapse and improve survival, and MRD-negative patients are safely spared adjuvant therapy in the major solid tumours."},"route":"/bottlenecks/b-dormancy-mrd/","neighbours":{"idea":[{"id":"idea-bio2-premetastatic-niche-assay","kind":"idea","name":"A blood test for the pre-metastatic niche","route":"/ideas/idea-bio2-premetastatic-niche-assay/"},{"id":"idea-bio2-marrow-niche-on-chip","kind":"idea","name":"A bone marrow niche on a chip to study human dormancy","route":"/ideas/idea-bio2-marrow-niche-on-chip/"},{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","route":"/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/"},{"id":"idea-bio2-mrd-clinic-service","kind":"idea","name":"A dedicated clinic for people whose blood test says the cancer is back","route":"/ideas/idea-bio2-mrd-clinic-service/"},{"id":"idea-bio2-dormancy-selective-screen","kind":"idea","name":"A drug screen that only rewards killing sleeping cancer cells","route":"/ideas/idea-bio2-dormancy-selective-screen/"},{"id":"idea-bio2-national-mrd-platform","kind":"idea","name":"A national platform trial that every ctDNA-positive patient can join","route":"/ideas/idea-bio2-national-mrd-platform/"},{"id":"idea-moon-mrd-weather-service","kind":"idea","name":"A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled","route":"/ideas/idea-moon-mrd-weather-service/"},{"id":"idea-bio2-survivor-plasma-biobank","kind":"idea","name":"Bank yearly blood from cancer survivors so future tests can be validated","route":"/ideas/idea-bio2-survivor-plasma-biobank/"},{"id":"idea-bio2-autophagy-block-mrd","kind":"idea","name":"Block the recycling that keeps dormant cells alive","route":"/ideas/idea-bio2-autophagy-block-mrd/"},{"id":"idea-bio2-il1-awakening-blockade","kind":"idea","name":"Blunt the inflammation that wakes sleeping cancer cells","route":"/ideas/idea-bio2-il1-awakening-blockade/"},{"id":"idea-bio2-net-blockade-perioperative","kind":"idea","name":"Break the neutrophil DNA nets that catch tumour cells after surgery","route":"/ideas/idea-bio2-net-blockade-perioperative/"},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/"},{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/"},{"id":"idea-ctdna-guided-adjuvant-melanoma","kind":"idea","name":"ctDNA-guided adjuvant therapy in stage II-III 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clonoSEQ)","route":"/technologies/ctdna-lymphoma-monitoring/"},{"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/"},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"}],"drug":[{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"company":[{"id":"adaptive-biotechnologies","kind":"company","name":"Adaptive Biotechnologies","route":"/companies/adaptive-biotechnologies/"},{"id":"foresight-diagnostics","kind":"company","name":"Foresight Diagnostics","route":"/companies/foresight-diagnostics/"},{"id":"guardant-health","kind":"company","name":"Guardant 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