{"entity":{"id":"idea-tr2-synergy-ranking-engine","kind":"idea","name":"An open engine that ranks every drug pair by predicted synergy before anyone runs a trial","aka":[],"tldr":"Use existing cell-line and organoid data to score thousands of drug pairs, publish the ranking openly, and only test the top of the list in people.","summary":"DepMap dependency screens, the NCI ALMANAC pairwise matrix and published organoid drug-response sets contain far more combination signal than has been mined. A public model that predicts synergy and, critically, therapeutic window (tumour versus normal-cell toxicity) for each pair in each molecular context would give trialists a prioritised shortlist. Models should be scored prospectively against every new combination readout.","asOf":"2026-09-08","links":[{"label":"DepMap portal","url":"https://depmap.org/portal/"},{"label":"NCI ALMANAC","url":"https://dtp.cancer.gov/ncialmanac"},{"label":"DREAM Challenges","url":"https://dreamchallenges.org/"}],"tags":[],"related":["depmap","drugbank-chembl","idea-organoid-guided-adc"],"cancers":[],"sections":[],"technologies":["crispr-screens","organoids","ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations in the top decile of the published ranking will show randomised phase 2 success (meeting primary endpoint) at least twice as often as combinations chosen by conventional mechanistic argument.","rationale":"The DREAM AstraZeneca-Sanger synergy challenge showed predictive signal in cell lines. NCI ALMANAC identified bortezomib plus clofarabine from a systematic screen. The failure has been that rankings are not published, not maintained and not scored against outcomes.","test":"Publish rankings for all pairs of approved oncology drugs; register predictions; score them against every randomised combination readout over three years, reporting calibration publicly.","maturity":"preclinical-evidence","actor":"data","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr2-synergy-ranking-engine/","neighbours":{"collection":[{"id":"depmap","kind":"collection","name":"DepMap (Cancer Dependency Map)","route":"/collections/depmap/"},{"id":"drugbank-chembl","kind":"collection","name":"DrugBank & ChEMBL","route":"/collections/drugbank-chembl/"}],"idea":[{"id":"idea-tr2-organoid-matrix-atlas","kind":"idea","name":"A public atlas of drug-pair responses across a thousand patient-derived organoids","route":"/ideas/idea-tr2-organoid-matrix-atlas/"},{"id":"idea-tr2-combination-forecast-tournament","kind":"idea","name":"An open forecasting tournament on which combination trials will succeed","route":"/ideas/idea-tr2-combination-forecast-tournament/"},{"id":"idea-organoid-guided-adc","kind":"idea","name":"Patient-derived organoids to pick ADC payloads","route":"/ideas/idea-organoid-guided-adc/"}],"technology":[{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","route":"/technologies/ai-drug-design/"},{"id":"crispr-screens","kind":"technology","name":"CRISPR functional genomics","route":"/technologies/crispr-screens/"},{"id":"organoids","kind":"technology","name":"Patient-derived organoids","route":"/technologies/organoids/"}],"bottleneck":[{"id":"b-preclinical-models","kind":"bottleneck","name":"Lab models that fail to predict what happens in patients","route":"/bottlenecks/b-preclinical-models/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"}]}}