# A drug screen that only rewards killing sleeping cancer cells

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

## TL;DR

Nearly all cancer drugs are found by killing fast-growing cells. Sleeping cells survive them. A screen designed around dormant cells would find a different class of drug.

## Summary

Dormant disseminated tumour cells are non-cycling, so proliferation-based screens are blind to them. Induced-dormancy models exist (serum-starved and matrix-confined cells, bone-marrow-niche co-cultures, three-dimensional dormancy assays) and small screens have already flagged cardiac glycosides, autophagy inhibitors and specific metabolic dependencies. Nobody has run a million-compound campaign with dormancy-selective killing as the primary readout.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: A dormancy-selective screen yields compounds that kill non-cycling disseminated tumour cells at least ten times more potently than cycling cells, a selectivity profile absent from current oncology libraries.
- Rationale: Screening paradigm determines drug class: kinase inhibitors dominate because proliferation assays reward them. Anti-persister screening in bacteriology produced genuinely new antibiotic chemistry by the same logic.
- Proposed test: Build and openly publish a validated dormancy assay pair (dormant versus cycling isogenic cells), screen an approved-drug library plus 100,000 diverse compounds, and report all hit and miss data.
- 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

- collections: [DepMap (Cancer Dependency Map)](https://onco.cc/collections/depmap/), [DrugBank & ChEMBL](https://onco.cc/collections/drugbank-chembl/)
- technologies: [CRISPR functional genomics](https://onco.cc/technologies/crispr-screens/), [Functional (ex vivo) drug testing](https://onco.cc/technologies/functional-drug-testing/), [Patient-derived organoids](https://onco.cc/technologies/organoids/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Lab models that fail to predict what happens in patients](https://onco.cc/bottlenecks/b-preclinical-models/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)

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