ideasIdea
Every drug screen includes standard reference compounds whose performance is published
Labs testing new cancer compounds should always include a few well-known drugs as controls and report how those behaved, so results from different labs can be compared.
Drug sensitivity results for the same cell line and drug differ substantially between large screens (the CCLE versus GDSC discordance). A defined panel of reference compounds (with expected potency ranges per reference cell line) included in every published screen, and reported in a standard format, would allow cross-study calibration and reveal systematic differences in assay conditions.
Hypothesis
Including reference panels will let discordant screens be reconciled by calibration, reducing cross-study potency disagreement by at least half for the drugs and lines covered.
Rationale
Clinical laboratories use internal standards in every run; preclinical pharmacology mostly does not, and the resulting variance has been quantified.
What would test it
Define the panel; run it in five laboratories under their standard conditions; test whether calibration reconciles their results on a shared set of new compounds.
Maturity
speculative
Who has to act
research
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks
- Preclinical results do not reproduce · Fewer than half of landmark cancer biology findings reproduce when someone else tries.
- Preclinical models that do not predict people · Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.