# Block the recycling that keeps dormant cells alive

Source: https://onco.cc/ideas/idea-bio2-autophagy-block-mrd/  
OnCo record `idea-bio2-autophagy-block-mrd` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

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

## Sources

- Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022): https://doi.org/10.1056/NEJMoa2200075

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Everolimus](https://onco.cc/drugs/everolimus/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- terms: [Late recurrence](https://onco.cc/terms/late-recurrence/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/)

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