# Keep dormant cells asleep instead of trying to kill them

Source: https://onco.cc/ideas/idea-bio2-pro-dormancy-therapy/  
OnCo record `idea-bio2-pro-dormancy-therapy` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022): https://doi.org/10.1056/NEJMoa2200075

## Connected records

- cancers: [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/)
- terms: [Late recurrence](https://onco.cc/terms/late-recurrence/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/)

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