Abstract

Circulating tumor cells (CTCs) are tumor cells found in the peripheral blood that putatively originate from established sites of malignancy and likely have metastatic potential. Analysis of CTCs has demonstrated promise as a prognostic marker as well as a source of identifying potential targets for novel therapeutics. Isolation and characterization of these cells for study, however, remain challenging owing to their rarity in comparison with other cellular components of the peripheral blood. Several techniques that exploit the unique biochemical properties of CTCs have been developed to facilitate their isolation. Positive selection of CTCs has been achieved using microfluidic surfaces coated with antibodies against epithelial cell markers or tumor-specific antigens such as EpCAM or prostate-specific membrane antigen (PSMA). Following isolation, characterization of CTCs may help guide clinical decision making. For instance, molecular and genetic characterization may shed light on the development of chemotherapy resistance and mechanisms of metastasis without the need for a tissue biopsy. This paper will review novel isolation techniques to capture CTCs from patients with advanced prostate cancer, as well as efforts to characterize the CTCs. We will also review how these analyzes can assist in clinical decision making. Conclusion: The study of CTCs provides insight into the molecular biology of tumors of prostate origin that will eventually guide the development of tailored therapeutics. These advances are predicated on high yield and accurate isolation techniques that exploit the unique biochemical features of these cells.

Highlights

  • Tumor metastases are a major cause of cancer morbidity and mortality

  • Circulating tumor cells (CTCs) are tumor cells found in the peripheral blood that putatively originate from established sites of malignancy and likely have metastatic potential

  • Circulating tumor cells (CTCs), which were first detected in the blood of an autopsy patient who died from cancer in 1869, are thought to represent tumor cells in transit, some of which will result in metastases (Ashworth, 1869)

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Summary

Introduction

Tumor metastases are a major cause of cancer morbidity and mortality. The precise mechanisms underlying the development of metastases, remain poorly understood. Circulating tumor cells (CTCs), which were first detected in the blood of an autopsy patient who died from cancer in 1869, are thought to represent tumor cells in transit, some of which will result in metastases (Ashworth, 1869). CTCs conceptually provide insight into the biology of a patient’s tumor that may facilitate the development of new therapeutic options and enable clinicians to tailor therapy to an individual patient in a longitudinal fashion (van de Stolpe et al, 2011). It follows that CTC isolation can replace biopsies and noninvasively yield valuable information about the evolving status of a patient’s disease

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