Cancer micrometastasis and tumour dormancy

Abstract

Many epithelial cancers carry a poor prognosis even after curative resection of early stage tumours. Tumour progression in these cancer patients has been attributed to the existence and persistence of disseminated tumour cells (DTC) in various body compartments as a sign of minimal residual disease. Bone marrow (BM) has been shown to be a common homing organ and reservoir for DTC. A significant correlation between the presence of DTC in BM and metastatic relapse has been reported in various tumour types. However, only a portion of patients with DTC in BM at primary surgery relapse. Thus far, little is known about the conditions required for the persistence of dormancy or the escape from the dormant phase into the active phase of metastasis formation. Thereby, this peculiar stage of conceivably balanced tumour cell division and death may last for decades in cancer patients. Most likely, the ability of a dormant DTC to "be activated" is a complex process involving (i) somatic aberrations in the tumour cells, (ii) the interaction of the DTC with the new microenvironment at the secondary site, and (iii) hereditary components of the host (i.e., cancer patient). In this review, we will summarize the key findings of research on micrometastatic cancer cells and discuss these findings in the context of the concept of tumour dormancy.