Micrometastatic disease and metastatic outgrowth: clinical issues and experimental approaches

Metastasis from the primary tumor to distant organs is the principal cause of mortality in patients with cancer. While prognostic factors can predict which patients are likely to have their cancer recur, these are not perfect predictors, and some patient's cancers recur even decades after apparently successful treatment. This phenomenon is referred to as dormancy. Data from experimental studies have revealed two categories of metastatic dormancy: cellular dormancy, with solitary cancer cells in cell-cycle arrest; and micrometastatic dormancy, characterized by a balanced state of proliferation and apoptosis, but with no net increase in size. Development of new models and imaging techniques to track the fate of dormant cancer cells is beginning to shed some light on dormancy. Elucidation of the molecular pathways involved in dormancy will advance clinical understanding and may suggest new avenues for treatment to inhibit the revival of these dormant cells, thereby reducing cancer mortality rates.