{"entity":{"id":"idea-moon-dormancy-eradication-programme","kind":"idea","name":"Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells","aka":[],"tldr":"Many relapses come from cancer cells that hid dormant for years. Find drugs that either force them awake so chemotherapy kills them, or keep them asleep for life.","summary":"Disseminated tumour cells in bone marrow and other niches survive therapy in a quiescent state maintained by niche signals (TGF-beta 2, BMP, NR2F1, autophagy) and cause late relapse in breast, prostate and melanoma. Preclinical work shows both awakening strategies (sensitising to chemotherapy) and dormancy-enforcing strategies (NR2F1 agonists, 5-azacytidine plus retinoic acid, CDK4/6 inhibitors) can reduce metastasis. The proposal is a coordinated programme: standardised dormant-cell models, biomarkers of dormancy burden in patients (bone marrow and ctDNA), and adjuvant trials of dormancy-directed therapy in patients with detected disseminated cells.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate","melanoma"],"sections":[],"technologies":["cdk46-inhibitor","epigenetic-drugs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dormancy-directed adjuvant regimen reduces late relapse (beyond three years) in high-risk hormone-receptor-positive breast cancer by a third compared with standard endocrine therapy.","rationale":"Late relapse is the dominant failure mode in several common cancers and no current therapy targets the dormant state; the biology is now tractable and measurable.","test":"Phase 2 randomised trial in patients with detectable disseminated tumour cells after standard adjuvant therapy, with disseminated cell clearance and distant recurrence as endpoints.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":10},"route":"/ideas/idea-moon-dormancy-eradication-programme/","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":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"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/"}]}}