Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy

Accumulating evidence indicates that cancer cells spread much earlier than was previously believed. Recent technological advances have greatly improved the detection methods of circulating tumour cells ( CTC s), suggesting that the dissemination of cancer cells into the circulation occurs randomly. Most CTC s die in circulation as a result of shear stress and/or anoikis. However, the persistence of disseminated tumour cells ( DTC s) in the bone marrow is the result of interaction of DTC s with bone marrow microenvironment. DTC s in the bone marrow undergo successive clonal expansions and a parallel progression that leads to new variants. Compared to the CTC s, DTC s in the bone marrow have a unique signature, which displayed dormant, mesenchymal phenotype and osteoblast‐like or osteoclast‐like phenotype. The persistence of DTC s in the bone marrow is always related to minimal residual diseases ( MRD s). This review outlines the difference between CTC s and DTC s in the bone marrow and describes how this difference affects the clinical values of CTC s and DTC s, such as metastasis and recurrence. We suggest that DTC s remaining in the bone marrow after therapy can be used as a superior marker in comparison with CTC s to define patients with an unfavourable prognosis and may therefore be a potential prognostic factor and therapeutic target for cancer therapy.