{"entity":{"id":"idea-dtc-colonisation-determinants","kind":"idea","name":"What decides which disseminated cells ever colonise?","aka":[],"tldr":"Most cancer cells that spread die or sleep forever; a few grow into lethal metastases. Nobody can yet tell them apart, and doing so would show whom to treat after surgery.","summary":"This open question asks what decides which disseminated cancer cells ever colonise: most die or sleep forever, a few grow into lethal metastases, and nobody can yet tell them apart. Bone marrow Disseminated tumour cells (DTCs) are common yet Late recurrence is uncommon; candidates include stemness programmes, niche interactions, immune surveillance and stochastic awakening (see Tumour dormancy). The hypothesis is that a measurable DTC state at surgery predicts late metastasis independently of stage and could be targeted with dormancy-enforcing therapy. The test is single-cell DTC profiling plus serial ctDNA in stage II-III breast cancer, relevant to HR-positive / HER2-negative breast cancer, Triple-negative breast cancer (TNBC) and Prostate cancer.","asOf":"2026-09-08","links":[{"label":"Massague and Obenauf, Metastatic colonisation by circulating tumour cells (Nature 2016)","url":"https://doi.org/10.1038/nature17038"}],"tags":["mechanism","open-question"],"related":[],"cancers":["breast-hr-positive","tnbc","prostate"],"sections":[],"technologies":["mrd-testing","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":["mount-sinai","mskcc","cold-spring-harbor"],"pathways":["metastatic-cascade","tumor-dormancy"],"terms":["disseminated-tumor-cells","late-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-massague-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A measurable DTC state (e.g., NR2F1-low, proliferation-primed, immune-evasive) present at surgery predicts late metastasis independently of stage and could be targeted with dormancy-enforcing therapy.","rationale":"Aguirre-Ghiso's NR2F1 dormancy programme, MSK latency-competent cell work, and TRACERx show dissemination is early and heterogeneous; MRD assays now let DTC biology be followed clinically.","test":"Prospective cohort with bone marrow DTC single-cell profiling plus serial ctDNA in stage II-III breast cancer, correlating DTC state with 10-year distant recurrence; nested randomised dormancy-maintenance trial (5-azacytidine + ATRA) in DTC-positive patients.","maturity":"preclinical-evidence"},"route":"/ideas/idea-dtc-colonisation-determinants/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"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":"metastatic-cascade","kind":"pathway","name":"The metastatic cascade","route":"/pathways/metastatic-cascade/"},{"id":"tumor-dormancy","kind":"pathway","name":"Tumour dormancy","route":"/pathways/tumor-dormancy/"}],"term":[{"id":"disseminated-tumor-cells","kind":"term","name":"Disseminated tumour cells (DTCs)","route":"/terms/disseminated-tumor-cells/"},{"id":"late-recurrence","kind":"term","name":"Late recurrence","route":"/terms/late-recurrence/"}],"paper":[{"id":"paper-massague-nature","kind":"paper","name":"Metastatic colonization by circulating tumour cells","route":"/key-papers/paper-massague-nature/"}]}}