{"entity":{"id":"idea-bio2-pro-dormancy-therapy","kind":"idea","name":"Keep dormant cells asleep instead of trying to kill them","aka":[],"tldr":"If we cannot kill sleeping cancer cells, we could try to keep them asleep for life. That would turn residual cancer into a harmless passenger.","summary":"Dormancy is an active transcriptional programme involving NR2F1, SOX9, TGF-beta2 and retinoic acid signalling. Combination all-trans retinoic acid plus a hypomethylating agent restored NR2F1 and enforced dormancy in head and neck and breast models from the Aguirre-Ghiso group, and both drugs are approved and cheap. The clinical question is whether enforced dormancy is durable and tolerable for years.","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":["head-and-neck","breast-hr-positive","prostate"],"sections":[],"technologies":["epigenetic-drugs","mrd-testing"],"targets":[],"drugs":["azacitidine"],"companies":[],"institutions":[],"pathways":[],"terms":["late-recurrence","mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Low-dose retinoid plus hypomethylating therapy in ctDNA-positive survivors keeps ctDNA stable or falling and delays radiographic relapse compared with observation, without cumulative toxicity.","rationale":"Prostate and breast cancers already prove that decades-long dormancy is a natural state, so the biology has an existence proof. Pro-dormancy is also a lower bar than eradication and may be achievable with well-characterised generic agents.","test":"A randomised phase 2 in ctDNA-positive survivors with ctDNA trajectory as primary endpoint, plus marrow NR2F1 staining as pharmacodynamic proof of mechanism.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":9},"route":"/ideas/idea-bio2-pro-dormancy-therapy/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"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/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"azacitidine","kind":"drug","name":"Azacitidine","route":"/drugs/azacitidine/"}],"term":[{"id":"late-recurrence","kind":"term","name":"Late recurrence","route":"/terms/late-recurrence/"},{"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/"}]}}