Circulating tumor cells (CTCs) can be separated and characterized from normal hematopoietic cellular constituents by a variety of methods. Different strategies have included separation by physical characteristics, such as size or weight, or by biological characteristics, such as expression of epithelial or cancer-specific markers. Of the latter, rtPCR for epithelial-related gene message, such as cytokeratin, and immunoseparation techniques using monoclonal antibodies against epithelial cellular adhesion molecule, have gained the most widespread use in investigational and standard clinical application to date. Detection and monitoring of CTCs might be useful for screening, prognosis, prediction of response to therapy, or monitoring clinical course in patients with primary or metastatic cancer. Currently, monitoring patients with metastatic disease is the most practical application of CTCs. In this regard, several studies have demonstrated that approximately 50-70% of patients with metastatic breast, colon, and prostate cancers have elevated CTC levels, when evaluated using a highly automated immunomagnetic CTC assay system, designated CellSearch®. These studies demonstrate that elevated CTC levels prior to initiation of a new systemic therapy are associated with a worse prognosis than those that do not, and that persistently elevated or subsequent rising CTC levels strongly suggest that the therapeutic regimen with which the patient is being treated is not working. Similar results have been shown with rtPCR assays, although they are not as widely available for routine clinical use. New areas of research are directed toward developing more sensitive means of CTC detection and generating a variety of methods to characterize the molecular and biologic nature of CTCs, such as the status of hormone receptors, epidermal, and other growth factor receptor family members, and indications of stem-cell characteristics.
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