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Cancer micrometastases

Abstract

Early spread of tumor cells is usually undetected by current imaging technologies. In patients with cancer and no signs of overt metastases sensitive methods have been developed to detect circulating tumor cells (CTCs) in the peripheral blood and disseminated tumor cells (DTCs) in the bone marrow. These technologies can be classified into cytometric and/or immunological and molecular approaches. Interestingly, the bone marrow seems to be a common homing tissue for cells derived from various epithelial tumors, and level 1a data from European and US groups have confirmed the prognostic impact of DTCs in the bone marrow of patients with breast cancer. Sequential peripheral blood analyses, however, are more convenient than bone marrow analyses for patients with solid tumors, and many research groups are currently assessing the clinical use of CTCs for assessment of prognosis and monitoring of systemic therapy. Molecular characterization of DTCs and CTCs opens a new avenue for understanding cancer dormancy, and might contribute to the identification of metastatic stem cells with important implications for future therapies. This Review focuses on the clinical relevance of the latest research results on blood-borne cancer micrometastases in patients with cancer.

Key Points

  • Cytometric/immunological and molecular approaches are the major methods to detect single DTCs/CTCs within bone marrow or blood cells

  • These technologies provide the potential to monitor systemic tumor-cell dissemination as one of the first crucial steps in the metastatic cascade

  • Various clinical studies demonstrated level 1a evidence for an association between the presence of DTCs in bone marrow and postoperative metastatic relapse, particularly in patients with breast cancer

  • Many research groups are assessing the clinical use of CTC detection in the peripheral blood for prognosis prediction and real-time monitoring of systemic therapies, with promising results

  • The assessment and monitoring of therapeutic targets on CTCs (and probably DTCs) might become an important future diagnostic tool to guide treatment decisions before the onset of overt metastases

  • The molecular characterization of DTCs/CTCs might contribute to a greater understanding of cancer dormancy and the role of metastatic stem cells, with important implications for future therapies

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Figure 1: Model of tumor cell circulation and cancer dormancy.
Figure 2: Balance of factors regulating the onset of metastasis (escape of dormancy).

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft (PA 341/15-2), Deutsche Krebshilfe (10-2181-Pa) Bonn, Germany; and the European Commission (DISMAL-project, contract no. LSHC-CT-2005-018911).

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Correspondence to Klaus Pantel.

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Pantel, K., Alix-Panabières, C. & Riethdorf, S. Cancer micrometastases. Nat Rev Clin Oncol 6, 339–351 (2009). https://doi.org/10.1038/nrclinonc.2009.44

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