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.

Keywords:

• angiogenesis
• autophagy
• clinical trials
• coagulation
• immune-mediated dormancy
• magnetic resonance imaging
• micrometastatic disease
• minimal residual disease
• recurrence
• tumor dormancy

Financial & competing interests disclosure

The authors’ research on this topic is supported by grant no. W81XWH-06–2–0033, US Department of Defense Breast Cancer Research Program; grant no. 016506 from the Canadian Breast Cancer Research Alliance, with special funding support from the Canadian Breast Cancer Foundation and the Cancer Research Society; grant no. 42511 from the Canadian Institutes of Health; and an award from the Lloyd Carr-Harris Foundation. Patricia M McGowan is the recipient of a Postdoctoral Fellowship, and Jennifer M Kirstein is the recipient of a Studentship, both from the Translational Breast Cancer Research Training Program at the London Regional Cancer Program. Ann F Chambers is a Canada Research Chair in Oncology, supported by the Canada Research Chairs Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors’ research on this topic is supported by grant no. W81XWH-06–2–0033, US Department of Defense Breast Cancer Research Program; grant no. 016506 from the Canadian Breast Cancer Research Alliance, with special funding support from the Canadian Breast Cancer Foundation and the Cancer Research Society; grant no. 42511 from the Canadian Institutes of Health; and an award from the Lloyd Carr-Harris Foundation. Patricia M McGowan is the recipient of a Postdoctoral Fellowship, and Jennifer M Kirstein is the recipient of a Studentship, both from the Translational Breast Cancer Research Training Program at the London Regional Cancer Program. Ann F Chambers is a Canada Research Chair in Oncology, supported by the Canada Research Chairs Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.