{"entity":{"id":"idea-moon-automated-combination-discovery","kind":"idea","name":"Automated combination discovery: patient-sample screens feeding Bayesian platform trials","aka":[],"tldr":"There are far more possible drug combinations than can ever be tried in patients. Test thousands on living samples of real tumours, then feed only the winners into adaptive trials.","summary":"The combination space of approved and investigational cancer drugs is astronomically large; combinations reach the clinic through intuition and commercial convenience. Functional precision medicine (ex vivo drug testing on patient cells, EXALT trial in haematological malignancies) and high-throughput organoid screening make empirical combination discovery on patient material feasible. The proposal is an integrated pipeline: standardised ex vivo combination screens on fresh samples from trial participants, machine learning to prioritise synergistic and resistance-preventing pairs, and a standing Bayesian platform trial that adds and drops combination arms based on pipeline output.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-organoid-guided-adc"],"cancers":["aml","colorectal"],"sections":[],"technologies":["functional-drug-testing","organoids","ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pipeline-prioritised combinations achieve response rates in the platform at least double those of historically selected combinations in the same settings.","rationale":"Empirical screening beat rational design in antibiotics and in EXALT; connecting the screen directly to a trial closes the loop that has been missing.","test":"Run the pipeline in relapsed acute myeloid leukaemia and metastatic colorectal cancer for three years; compare platform response rates with contemporaneous conventional combination trials.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":6},"route":"/ideas/idea-moon-automated-combination-discovery/","neighbours":{"idea":[{"id":"idea-organoid-guided-adc","kind":"idea","name":"Patient-derived organoids to pick ADC payloads","route":"/ideas/idea-organoid-guided-adc/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","route":"/technologies/ai-drug-design/"},{"id":"functional-drug-testing","kind":"technology","name":"Functional (ex vivo) drug testing","route":"/technologies/functional-drug-testing/"},{"id":"organoids","kind":"technology","name":"Patient-derived organoids","route":"/technologies/organoids/"}],"term":[{"id":"basket-umbrella-platform","kind":"term","name":"Basket, umbrella, and platform trials","route":"/terms/basket-umbrella-platform/"}],"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/"}],"paper":[{"id":"paper-palmer-cell","kind":"paper","name":"Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy","route":"/key-papers/paper-palmer-cell/"}]}}