# Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models

Source: https://onco.cc/ideas/idea-moon-closed-loop-adaptive-therapy/  
OnCo record `idea-moon-closed-loop-adaptive-therapy` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Osimertinib](https://onco.cc/drugs/osimertinib/)
- institutions: [Moffitt Cancer Center](https://onco.cc/institutions/moffitt/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- trials: [A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participan](https://onco.cc/trials/nct06417814/), [ADAURA](https://onco.cc/trials/adaura/), [FLAURA](https://onco.cc/trials/flaura/), [FLAURA2](https://onco.cc/trials/flaura2/), [LAURA](https://onco.cc/trials/laura/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [AI that is built but not validated or deployed](https://onco.cc/bottlenecks/b-ai-validation/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- key papers: [FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-flaura-nejm-2018/), [Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer](https://onco.cc/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2017/), [Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC](https://onco.cc/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2020/)

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