Micrometastatic Disease and Metastatic Outgrowth: Clinical Issues and Experimental Approaches

Abstract

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.

Temporal and Spatial Cooperation of Snail1 and Twist1 during Epithelial–Mesenchymal Transition Predicts for Human Breast Cancer Recurrence

“…Experimental work has suggested that rate-limiting steps in metastasis are the ability of dormant tumor cells to resist initial systemic therapy, remain viable in a foreign tissue, and reactivate proliferation when suitable conditions are present (39, 40). Evidence for clinically silent residual disease, such as blood borne circulating tumor cells (CTCs) or disseminated tumor cells (DTCs) in bone marrow (BM), for example, has been found in clinically cancer-free patients (41–43).…”

Autophagy in cancer metastasis

“…The metastatic cascade can be divided into a series of stages: local invasion, intravasation, survival in the circulation, extravasation, survival at a second site and finally outgrowth at a second site (14, 15)(Figure 1). All of these steps involve the physical translocation of cancer cells to new microenvironments, where they must survive altered nutrient, growth factor and physical support in order to colonize successfully (16).…”

The potential for liquid biopsies in the precision medical treatment of breast cancer

“…Thus deep sequencing of plasma DNA, applied to selected samples with high tumor burden in blood, may help identify the mutations associated with drug resistance 193,219 .…”