{"entity":{"id":"idea-bio2-autophagy-block-mrd","kind":"idea","name":"Block the recycling that keeps dormant cells alive","aka":[],"tldr":"Sleeping cancer cells survive by recycling their own contents. An old malaria drug blocks that recycling and is being tested in people with no visible cancer but detectable residual cells.","summary":"Dormant disseminated cells depend on autophagy for survival, and hydroxychloroquine plus mTOR inhibition has been tested in bone-marrow-positive breast cancer survivors in the CLEVER-type design at Johns Hopkins. The concept is attractive because it treats survivors while disease burden is at its minimum, but hydroxychloroquine is a weak, non-specific autophagy inhibitor; a potent selective ULK1 or ATG7 inhibitor would be the real test.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":["everolimus"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["mrd","late-recurrence"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Selective autophagy inhibition clears bone-marrow disseminated tumour cells or converts ctDNA-positive survivors to ctDNA-negative at a materially higher rate than observation.","rationale":"Autophagy dependence is a well-documented feature of quiescent, nutrient-poor cells, and dormancy is the setting where selective vulnerability should be largest. The endpoint is molecular and cheap, so a small trial can give a clear answer.","test":"A randomised phase 2 in ctDNA-positive or marrow-positive survivors comparing selective autophagy inhibition with observation, primary endpoint molecular clearance at 12 months, with serial marrow and plasma sampling.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-autophagy-block-mrd/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"everolimus","kind":"drug","name":"Everolimus","route":"/drugs/everolimus/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"}],"term":[{"id":"late-recurrence","kind":"term","name":"Late recurrence","route":"/terms/late-recurrence/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/"}]}}