# What decides which disseminated cells ever colonise?

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

## TL;DR

Most cancer cells that spread die or sleep forever; a few grow into lethal metastases. Nobody can yet tell them apart, and doing so would show whom to treat after surgery.

## Summary

This open question asks what decides which disseminated cancer cells ever colonise: most die or sleep forever, a few grow into lethal metastases, and nobody can yet tell them apart. Bone marrow Disseminated tumour cells (DTCs) are common yet Late recurrence is uncommon; candidates include stemness programmes, niche interactions, immune surveillance and stochastic awakening (see Tumour dormancy). The hypothesis is that a measurable DTC state at surgery predicts late metastasis independently of stage and could be targeted with dormancy-enforcing therapy. The test is single-cell DTC profiling plus serial ctDNA in stage II-III breast cancer, relevant to HR-positive / HER2-negative breast cancer, Triple-negative breast cancer (TNBC) and Prostate cancer.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- Hypothesis: A measurable DTC state (e.g., NR2F1-low, proliferation-primed, immune-evasive) present at surgery predicts late metastasis independently of stage and could be targeted with dormancy-enforcing therapy.
- Rationale: Aguirre-Ghiso's NR2F1 dormancy programme, MSK latency-competent cell work, and TRACERx show dissemination is early and heterogeneous; MRD assays now let DTC biology be followed clinically.
- Proposed test: Prospective cohort with bone marrow DTC single-cell profiling plus serial ctDNA in stage II-III breast cancer, correlating DTC state with 10-year distant recurrence; nested randomised dormancy-maintenance trial (5-azacytidine + ATRA) in DTC-positive patients.
- Maturity: preclinical-evidence

## Sources

- Massague and Obenauf, Metastatic colonisation by circulating tumour cells (Nature 2016): https://doi.org/10.1038/nature17038

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/), [The Mount Sinai Hospital / Tisch Cancer Institute](https://onco.cc/institutions/mount-sinai/)
- pathways: [The metastatic cascade](https://onco.cc/pathways/metastatic-cascade/), [Tumour dormancy](https://onco.cc/pathways/tumor-dormancy/)
- terms: [Disseminated tumour cells (DTCs)](https://onco.cc/terms/disseminated-tumor-cells/), [Late recurrence](https://onco.cc/terms/late-recurrence/)
- key papers: [Metastatic colonization by circulating tumour cells](https://onco.cc/key-papers/paper-massague-nature/)

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