{"entity":{"id":"tumor-dormancy","kind":"pathway","name":"Tumour dormancy","aka":[],"tldr":"Cancer cells can hide in bone marrow, lung, or brain for years or decades, asleep and invisible to scans and chemotherapy, then wake up. Late relapse in breast and prostate cancer is dormancy ending.","summary":"Disseminated tumour cells enter quiescence (p38-high/ERK-low, NR2F1, DYRK1A), are held by niche signals (TGF-β2, BMP7, endothelial thrombospondin) and immune surveillance (NK cells, T cells), and evade cytotoxics by not dividing. Awakening triggers include inflammation (neutrophil extracellular traps), ageing, surgery-induced wound healing, and loss of immune control. Extended endocrine therapy in ER+ breast cancer is de facto dormancy maintenance. Strategies: keep cells asleep (NR2F1 agonists, 5-azacytidine + retinoic acid pilot in prostate), wake and kill (with cell-cycle-dependent drugs), or clear them immunologically. MRD assays make dormancy measurable for the first time.","asOf":"2026-09-08","links":[{"label":"Phan & Croucher, The dormant cancer cell life cycle (Nature Reviews Cancer 2020)","url":"https://doi.org/10.1038/s41568-020-0263-0"},{"label":"Albrengues et al., Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells (Science 2018)","url":"https://doi.org/10.1126/science.aao4227"}],"tags":["mechanism"],"related":[],"cancers":["breast-hr-positive","prostate","melanoma"],"sections":[],"technologies":["mrd-testing","endocrine-therapy","cdk46-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":["mount-sinai","cold-spring-harbor","mskcc"],"pathways":["metastatic-cascade","clonal-evolution","tgf-beta","er-signaling"],"terms":["late-recurrence","disseminated-tumor-cells","mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-phan-nat-rev-cancer","paper-albrengues-science"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Aguirre-Ghiso (Einstein/Mount Sinai) on dormancy signalling and NR2F1; Egeblad (CSHL) on NETs awakening dormant cells; Massagué (MSK) on latency competent cells; Ghajar (Fred Hutch) on perivascular niches."],"analogy":"Seeds that stay in the soil for years waiting for the right spring. You can keep the ground cold (maintenance therapy), force them to sprout and mow them (wake-and-kill), or dig them out (immune clearance).","nodes":[{"id":"dtc","label":"Disseminated tumour cell","x":15,"y":50},{"id":"quies","label":"Quiescence (p38↑, ERK↓, NR2F1)","x":42,"y":30},{"id":"niche","label":"Niche: TGF-β2, BMP7, endothelium","x":42,"y":70},{"id":"immune","label":"NK / T-cell surveillance","x":15,"y":15},{"id":"wake","label":"Awakening: NETs, inflammation, ageing","x":70,"y":50},{"id":"relapse","label":"Late relapse","x":92,"y":50}],"edges":[{"from":"dtc","to":"quies","type":"activates"},{"from":"niche","to":"quies","type":"activates"},{"from":"immune","to":"dtc","type":"inhibits"},{"from":"wake","to":"quies","type":"inhibits"},{"from":"wake","to":"relapse","type":"activates"},{"from":"quies","to":"relapse","type":"inhibits"}],"interventions":["Extended adjuvant endocrine therapy and CDK4/6 inhibitors (de facto dormancy maintenance)","5-azacytidine + all-trans retinoic acid to enforce dormancy (pilot, prostate)","MRD-guided intervention at molecular relapse","NET/inflammation inhibitors to prevent awakening (preclinical)"]},"route":"/pathways/tumor-dormancy/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"institution":[{"id":"cold-spring-harbor","kind":"institution","name":"Cold Spring Harbor Laboratory","route":"/institutions/cold-spring-harbor/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"mount-sinai","kind":"institution","name":"The Mount Sinai Hospital / Tisch Cancer Institute","route":"/institutions/mount-sinai/"}],"pathway":[{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"},{"id":"lipid-metabolism-cancer","kind":"pathway","name":"Lipid synthesis, uptake & cholesterol","route":"/pathways/lipid-metabolism-cancer/"},{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"},{"id":"er-signaling","kind":"pathway","name":"Oestrogen receptor signalling","route":"/pathways/er-signaling/"},{"id":"organ-tropism-seed-soil","kind":"pathway","name":"Organ tropism: seed and soil","route":"/pathways/organ-tropism-seed-soil/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"metastatic-cascade","kind":"pathway","name":"The metastatic cascade","route":"/pathways/metastatic-cascade/"},{"id":"pre-metastatic-niche","kind":"pathway","name":"The pre-metastatic niche","route":"/pathways/pre-metastatic-niche/"}],"term":[{"id":"disseminated-tumor-cells","kind":"term","name":"Disseminated tumour cells (DTCs)","route":"/terms/disseminated-tumor-cells/"},{"id":"activating-invasion-metastasis","kind":"term","name":"Hallmark: activating invasion and metastasis","route":"/terms/activating-invasion-metastasis/"},{"id":"late-recurrence","kind":"term","name":"Late recurrence","route":"/terms/late-recurrence/"},{"id":"metastasis","kind":"term","name":"Metastasis","route":"/terms/metastasis/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"relapse-recurrence","kind":"term","name":"Recurrence and relapse","route":"/terms/relapse-recurrence/"},{"id":"seed-and-soil-hypothesis","kind":"term","name":"Seed and soil hypothesis of metastasis (Paget)","route":"/terms/seed-and-soil-hypothesis/"},{"id":"stem-cell","kind":"term","name":"Stem cell","route":"/terms/stem-cell/"}],"paper":[{"id":"paper-albrengues-science","kind":"paper","name":"Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice","route":"/key-papers/paper-albrengues-science/"},{"id":"paper-phan-nat-rev-cancer","kind":"paper","name":"The dormant cancer cell life cycle","route":"/key-papers/paper-phan-nat-rev-cancer/"}],"idea":[{"id":"idea-dormancy-maintenance-therapy","kind":"idea","name":"Keep them asleep: dormancy maintenance as adjuvant therapy","route":"/ideas/idea-dormancy-maintenance-therapy/"},{"id":"idea-dtc-colonisation-determinants","kind":"idea","name":"What decides which disseminated cells ever colonise?","route":"/ideas/idea-dtc-colonisation-determinants/"}],"target":[{"id":"bmp7","kind":"target","name":"BMP7","route":"/targets/bmp7/"}]}}