{"entity":{"id":"idea-moon-closed-loop-adaptive-therapy","kind":"idea","name":"Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models","aka":[],"tldr":"Rather than giving the same dose until the cancer grows, measure tumour DNA in blood every few weeks and let a validated algorithm raise, lower, pause or switch drugs to keep the cancer suppressed for longer.","summary":"Adaptive therapy trials in prostate cancer (PSA-guided abiraterone cycling at Moffitt) suggest that modulating dose to maintain competition between sensitive and resistant cells can extend control. Circulating tumour DNA now allows frequent, clone-resolved monitoring across cancers. The proposal is a closed-loop system: serial ctDNA and imaging feed an evolutionary model that recommends dose and drug changes under pre-specified rules, with clinician oversight, tested first in oncogene-driven lung cancer and hormone-sensitive prostate cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["nsclc","prostate"],"sections":[],"technologies":["liquid-biopsy","kinase-inhibitors"],"targets":[],"drugs":["osimertinib"],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":["ctdna","resistance"],"trials":["adaura","flaura","flaura2","laura","nct06417814"],"people":[],"bottlenecks":["b-resistance","b-dose-optimisation","b-ai-validation"],"keyPapers":["paper-flaura-nejm-2018","paper-osimertinib-nsclc-n-engl-j-med-2017","paper-osimertinib-nsclc-n-engl-j-med-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Algorithm-guided adaptive dosing extends time to treatment failure by at least 30% over continuous standard dosing with lower cumulative drug exposure and toxicity.","rationale":"Resistance is an evolutionary process; continuous maximum dosing selects for it. Frequent measurement plus rule-based modulation is how control engineering handles adaptive adversaries.","test":"Randomised phase 2 of closed-loop adaptive versus standard continuous therapy in EGFR-mutant lung cancer on osimertinib, with time to failure primary and cumulative dose and toxicity secondary.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},"route":"/ideas/idea-moon-closed-loop-adaptive-therapy/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"}],"institution":[{"id":"moffitt","kind":"institution","name":"Moffitt Cancer Center","route":"/institutions/moffitt/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"}],"trial":[{"id":"nct06417814","kind":"trial","name":"A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participan","route":"/trials/nct06417814/"},{"id":"adaura","kind":"trial","name":"ADAURA","route":"/trials/adaura/"},{"id":"flaura","kind":"trial","name":"FLAURA","route":"/trials/flaura/"},{"id":"flaura2","kind":"trial","name":"FLAURA2","route":"/trials/flaura2/"},{"id":"laura","kind":"trial","name":"LAURA","route":"/trials/laura/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-ai-validation","kind":"bottleneck","name":"AI that is built but not validated or deployed","route":"/bottlenecks/b-ai-validation/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"paper":[{"id":"paper-flaura-nejm-2018","kind":"paper","name":"FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-flaura-nejm-2018/"},{"id":"paper-osimertinib-nsclc-n-engl-j-med-2017","kind":"paper","name":"Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer","route":"/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2017/"},{"id":"paper-osimertinib-nsclc-n-engl-j-med-2020","kind":"paper","name":"Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC","route":"/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2020/"}]}}