# Dormant cells and minimal residual disease

Source: https://onco.cc/bottlenecks/b-dormancy-mrd/  
OnCo record `b-dormancy-mrd` (Bottleneck). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Bottleneck
- Last checked: 2026-09-08
- Stage: biology
- Severity: critical
- Metrics: Risk of distant recurrence in years 5-20 for ER-positive breast cancer after 5 years of endocrine therapy, by original stage: 10% to 41% (Pan et al., NEJM 2017); Adjuvant chemotherapy use with ctDNA-guided vs standard management in stage II colon cancer (DYNAMIC), with non-inferior recurrence-free survival: 15% vs 28% (Tie et al., NEJM 2022)
- 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.

## Sources

- Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022): https://doi.org/10.1056/NEJMoa2200075
- Pan et al., 20-year risks of breast-cancer recurrence (NEJM 2017): https://doi.org/10.1056/NEJMoa1701830
- Phan & Croucher, The dormant cancer cell life cycle (Nature Reviews Cancer 2020): https://doi.org/10.1038/s41568-020-0263-0

## Connected records

- ideas: [A blood test for the pre-metastatic niche](https://onco.cc/ideas/idea-bio2-premetastatic-niche-assay/), [A bone marrow niche on a chip to study human dormancy](https://onco.cc/ideas/idea-bio2-marrow-niche-on-chip/), [A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection](https://onco.cc/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/), [A dedicated clinic for people whose blood test says the cancer is back](https://onco.cc/ideas/idea-bio2-mrd-clinic-service/), [A drug screen that only rewards killing sleeping cancer cells](https://onco.cc/ideas/idea-bio2-dormancy-selective-screen/), [A national platform trial that every ctDNA-positive patient can join](https://onco.cc/ideas/idea-bio2-national-mrd-platform/), [A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled](https://onco.cc/ideas/idea-moon-mrd-weather-service/), [Bank yearly blood from cancer survivors so future tests can be validated](https://onco.cc/ideas/idea-bio2-survivor-plasma-biobank/), [Block the recycling that keeps dormant cells alive](https://onco.cc/ideas/idea-bio2-autophagy-block-mrd/), [Blunt the inflammation that wakes sleeping cancer cells](https://onco.cc/ideas/idea-bio2-il1-awakening-blockade/), [Break the neutrophil DNA nets that catch tumour cells after surgery](https://onco.cc/ideas/idea-bio2-net-blockade-perioperative/), [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/), [ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-crc/), [ctDNA-guided adjuvant therapy in stage II-III melanoma](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-melanoma/), [ctDNA-triggered escalation in early TNBC](https://onco.cc/ideas/idea-ctdna-escalation-tnbc/), [Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer](https://onco.cc/ideas/idea-moon-engineered-immune-surveillance/), [Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells](https://onco.cc/ideas/idea-moon-dormancy-eradication-programme/), [Flush dormant cells out of bone marrow, then kill them](https://onco.cc/ideas/idea-bio2-cxcr4-mobilise-then-kill/), [Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials](https://onco.cc/ideas/idea-tr2-ctdna-mrd-qualification/), [Intercepting late recurrence with ctDNA surveillance and oral SERDs](https://onco.cc/ideas/idea-late-recurrence-interception/), [Keep dormant cells asleep instead of trying to kill them](https://onco.cc/ideas/idea-bio2-pro-dormancy-therapy/), [Kill the sleeping survivor cells with iron-dependent cell death](https://onco.cc/ideas/idea-bio1-persister-ferroptosis/), [MRD-guided treatment-free intervals in myeloma](https://onco.cc/ideas/idea-mrd-guided-stop-myeloma/), [Off-the-shelf natural killer cells to sweep up residual disease](https://onco.cc/ideas/idea-bio2-nk-cells-for-mrd/), [Pay for residual disease tests only inside a trial or registry](https://onco.cc/ideas/idea-bio2-mrd-coverage-with-evidence/), [Personalised cancer vaccines at commodity cost through fully automated manufacturing](https://onco.cc/ideas/idea-moon-neoantigen-vaccines-at-scale/), [Personalised vaccines given only when the blood test turns positive](https://onco.cc/ideas/idea-bio2-mrd-triggered-neoantigen-vaccine/), [Push residual disease detection a hundredfold deeper with whole-genome methods](https://onco.cc/ideas/idea-bio2-whole-genome-mrd-depth/), [Read the spinal fluid to track brain tumours without opening the skull](https://onco.cc/ideas/idea-bio2-csf-ctdna-monitoring/), [Reference materials and open proficiency testing for residual disease tests](https://onco.cc/ideas/idea-bio2-mrd-reference-standards/), [Starve the survivors: target the energy pathway drug-tolerant cells switch to](https://onco.cc/ideas/idea-bio1-persister-metabolic-vulnerability/), [Strip the platelet coat off travelling tumour cells in ctDNA-positive patients](https://onco.cc/ideas/idea-bio2-platelet-cloak-aspirin-mrd/), [Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps](https://onco.cc/ideas/idea-crc-ctdna-de-escalation-beyond-stage-ii/), [Take the blood test, and give the drug, at the right time of day](https://onco.cc/ideas/idea-bio2-circadian-mrd-sampling/), [Ten-year awards for scientists who commit to one hard problem](https://onco.cc/ideas/idea-fund-ten-year-hard-problem-awards/), [Use circulating tumour DNA instead of the interim scan to decide what happens next](https://onco.cc/ideas/lymphoma-ev-ctdna-instead-of-the-interim-scan/), [Use residual disease tests to decide who needs ten years of hormone therapy](https://onco.cc/ideas/idea-bio2-mrd-guided-endocrine-duration/), [When the blood test is positive, hunt for the lesion with sensitive imaging](https://onco.cc/ideas/idea-bio2-localise-the-mrd/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [ctDNA monitoring in lymphoma (PhasED-seq, clonoSEQ)](https://onco.cc/technologies/ctdna-lymphoma-monitoring/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/)
- drugs: [Signatera](https://onco.cc/drugs/signatera/)
- companies: [Adaptive Biotechnologies](https://onco.cc/companies/adaptive-biotechnologies/), [Foresight Diagnostics](https://onco.cc/companies/foresight-diagnostics/), [Guardant Health](https://onco.cc/companies/guardant-health/), [Natera](https://onco.cc/companies/natera/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Late recurrence](https://onco.cc/terms/late-recurrence/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)](https://onco.cc/terms/mrd-negativity-myeloma/), [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- trials: [CAMBRIA-1 & CAMBRIA-2](https://onco.cc/trials/cambria/), [CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)](https://onco.cc/trials/circulate-japan/), [DYNAMIC](https://onco.cc/trials/dynamic/), [IMvigor011](https://onco.cc/trials/imvigor011/), [NATALEE](https://onco.cc/trials/natalee/)
- key papers: [20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years](https://onco.cc/key-papers/paper-pan-n-engl-j-med/), [ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-adaura-nejm-2020/), [Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)](https://onco.cc/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/), [Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy](https://onco.cc/key-papers/paper-create-x-adjuvant-capecitabine-nejm-2017/), [Alectinib in resected ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-wu-alina-adjuvant-alectinib-nejm-2024/), [Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial](https://onco.cc/key-papers/paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020/), [CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint](https://onco.cc/key-papers/paper-cepheus-dara-vrd-natmed-2025/), [CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery](https://onco.cc/key-papers/paper-checkmate-816-nejm-2022/), [Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer](https://onco.cc/key-papers/paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016/), [CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients](https://onco.cc/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/), [Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection](https://onco.cc/key-papers/paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025/), [Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumour DNA](https://onco.cc/key-papers/paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016/), [DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer](https://onco.cc/key-papers/paper-dynamic-nejm-2022/), [ECOG-ACRIN E1910: adding blinatumomab to chemotherapy for adults with B-cell ALL already in MRD-negative remission](https://onco.cc/key-papers/paper-e1910-blinatumomab-mrd-negative-all-nejm-2024/), [GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold](https://onco.cc/key-papers/paper-galaxy-signatera-nat-med-2023/), [IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery](https://onco.cc/key-papers/paper-imvigor011-nejm-2025/), [KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment](https://onco.cc/key-papers/paper-katherine-nejm-2019/), [KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer](https://onco.cc/key-papers/paper-keynote-522-nejm-2022/), [KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery](https://onco.cc/key-papers/paper-keynote-564-nejm-2021/), [Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group](https://onco.cc/key-papers/paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008/), [monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer](https://onco.cc/key-papers/paper-monarche-jco-2020/), [MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL](https://onco.cc/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/), [NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer](https://onco.cc/key-papers/paper-natalee-nejm-2024/), [NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer](https://onco.cc/key-papers/paper-niagara-nejm-2024/), [OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer](https://onco.cc/key-papers/paper-olympia-nejm-2021/), [PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours](https://onco.cc/key-papers/paper-paola-1-nejm-2019/), [Perioperative durvalumab for resectable non-small-cell lung cancer](https://onco.cc/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/), [PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma](https://onco.cc/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/), [Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution](https://onco.cc/key-papers/paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017/), [Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission](https://onco.cc/key-papers/paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999/), [Real-world analysis of ctDNA and other biomarkers in patients with curatively resected stage I-III biliary tract cancer](https://onco.cc/key-papers/paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026/), [Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer](https://onco.cc/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/), [SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer](https://onco.cc/key-papers/paper-solo-1-nejm-2018/), [The dormant cancer cell life cycle](https://onco.cc/key-papers/paper-phan-nat-rev-cancer/), [TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse](https://onco.cc/key-papers/paper-tracerx-evolution-nature-2023/), [TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse](https://onco.cc/key-papers/paper-tracerx-100-nejm-2017/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/), [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/), [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- institutions: [Centre Oscar Lambret](https://onco.cc/institutions/centre-oscar-lambret/)
- pathways: [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Intravasation & circulating tumour cells](https://onco.cc/pathways/intravasation-ctc-survival/)

---
JSON: https://onco.cc/api/v1/entities/b-dormancy-mrd.json