{"entity":{"id":"idea-bio1-collateral-sensitivity-atlas","kind":"idea","name":"An open atlas of collateral sensitivity for every approved targeted drug","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["functional-drug-testing","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For most approved targeted agents, at least one collateral sensitivity with a greater than three-fold shift will be reproducible across models and will translate into a sequencing rule that prolongs second-line response in a trial.","rationale":"Resistance carries costs. Antibiotic collateral sensitivity maps have already guided cycling regimens; oncology has the models and drugs but has never done the systematic screen.","test":"Two-year screen across 20 drugs and 200 models with independent replication of top hits; then a randomised second-line sequencing trial in the setting with the strongest signal.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-collateral-sensitivity-atlas/","neighbours":{"technology":[{"id":"crispr-screens","kind":"technology","name":"CRISPR functional genomics","route":"/technologies/crispr-screens/"},{"id":"functional-drug-testing","kind":"technology","name":"Functional (ex vivo) drug testing","route":"/technologies/functional-drug-testing/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}