OnCo
ideasIdea

Make in vivo metastasis screens a required step in drug discovery

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.

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.

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.
What would test it
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
Who has to act
research
Cost to try
Small (under $1M)
Years to first evidence
4
Bottlenecks it attacks

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