An open atlas of collateral sensitivity for every approved targeted drug
When a tumour evolves resistance to one drug, it sometimes becomes weaker against another. Map these trade-offs systematically so doctors can pick the next drug to exploit them.
Collateral sensitivity is well characterised in antibiotics and shown in a few oncology examples (MEK-inhibitor resistance sensitising to certain agents, ABL inhibitor rotation in CML). A systematic programme would evolve resistance to each approved targeted agent in dozens of models, screen the resistant derivatives against the full pharmacopoeia, and publish a public sensitivity map to inform sequencing trials.
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
- Too many combinations to test · There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.
Pages like this
not linked directly; found by shared links- IdeaEvery resistance mechanism found in a patient must be rebuilt in the laboratory
Shares Functional (ex vivo) drug testing, CRISPR functional genomics, Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaBarcode patient-derived tumours to watch which clones win under each drug
Shares CRISPR functional genomics, Drug resistance (primary and acquired), Tumour heterogeneity and clonal evolution.
- PersonFrancisca Vazquez
Shares Broad Institute of MIT and Harvard, CRISPR functional genomics.
- IdeaFind the parts of a tumour the drug never reaches
Shares Drug resistance (primary and acquired), Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy.
- IdeaPause a failed drug so the tumour becomes sensitive to it again
Shares Drug resistance (primary and acquired), Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy.
- IdeaForecast the next resistance mutation like the weather
Shares Drug resistance (primary and acquired), Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy.
- IdeaCut off the emergency programme cancer cells use to survive treatment
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaDesign drug pairs where resisting one makes you vulnerable to the other
Shares Tumour heterogeneity and clonal evolution, Too many combinations to test, Acquired resistance to every therapy.