# Make in vivo metastasis screens a required step in drug discovery

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

## TL;DR

Drug candidates are tested for shrinking tumours, almost never for stopping spread. A standard spread test would find anti-metastatic drugs we are throwing away.

## Summary

Barcoded in vivo CRISPR and lineage-tracing screens can quantify seeding, survival in circulation and outgrowth as separate phenotypes. Very few programmes run them, so anti-metastatic activity is invisible during discovery. Funders could require a standard metastasis panel (spontaneous metastasis from orthotopic implantation plus a barcoded seeding assay) from any grant or programme claiming anti-metastatic intent.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Compounds active in standardised seeding and outgrowth assays but inactive in subcutaneous growth assays exist at a rate of at least 5% in current oncology libraries, and are being discarded today.
- Rationale: Metastasis is a distinct set of phenotypes with distinct genetic dependencies, so screening only for proliferation systematically selects against anti-metastatic mechanisms. Barcoded clonal tracking gives quantitative, well-powered readouts from few animals.
- Proposed test: Rescreen 2,000 shelved oncology compounds from academic and industry libraries in a barcoded orthotopic seeding assay for two tumour types, and publish all hits and misses openly.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019): https://doi.org/10.1002/cam4.2474

## Connected records

- collections: [Cancer Models (PDCM Finder) & HCMI](https://onco.cc/collections/cancer-models/), [DepMap (Cancer Dependency Map)](https://onco.cc/collections/depmap/)
- technologies: [CRISPR functional genomics](https://onco.cc/technologies/crispr-screens/), [Patient-derived organoids](https://onco.cc/technologies/organoids/), [Patient-derived xenografts](https://onco.cc/technologies/pdx-models/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Lab models that fail to predict what happens in patients](https://onco.cc/bottlenecks/b-preclinical-models/), [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/)
- key papers: [Are 90% of deaths from cancer caused by metastases?](https://onco.cc/key-papers/paper-dillekas-cancer-med/)

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