Isolation of rare circulating tumor cells in cancer patients: technical aspects and clinical implications

Abstract

Circulating tumor cells (CTCs) may be detected in the blood of patients with epithelial tumors using different analytical approaches. The relative number of CTCs is low and they include a heterogeneous population of cells with diverse biological and molecular characteristics, often different from those of the respective primary tumor. Until recently, they have been difficult to detect and, even though discordant results have been reported when different methods of detection were used, they may provide prognostic and predictive information. Several antibody- or molecular-based CTC detection methods have been developed, offering hope for individualized risk assessment by utilizing CTCs as biomarkers of disease progression and drug response. Pilot studies have also shown that by utilizing methods that permit, besides enumeration, a molecular characterization of CTCs, one could better identify high-risk patients, predict response to targeted therapies, analyze gene expression profiles (in order to identify new potential drug targets) and increase our knowledge of the metastatic process. In this article we review the techniques currently utilized for isolation and characterization of CTCs and we discuss their potential utility in clinical oncology focusing on the future perspectives in this field.

Keywords::

• biological characterization
• biomarker
• circulating tumor cell
• detection method
• metastasis
• solid tumor

Acknowledgements

We thank all the members of our laboratories for the research work. We gratefullly thank Sabina Merlo (Department of Electronic Engineering at the University of Pavia, Pavia, Italy) for critical discussion and helpful suggestions. We also thank Laurene Kelly for English revision of the manuscript.

Financial & competing interests disclosure

The work on circulating tumor cells performed by the authors was partly supported by a research grant from the Foundation IRCCS Policlinico San Matteo, Pavia, Italy, to Marco Danova. Giuliano Mazzini is the inventor of the recently patented technology for circulating tumor cell analysis MicroCount™. 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.