Circulating tumor cells: detection, molecular profiling and future prospects

Abstract

Disseminated malignancy is responsible for the vast majority of cancer-related deaths. During this process, circulating tumor cells (CTC) are generated, spread from the primary tumor, colonize distant organs and lead to overt metastatic disease. CTC are essential for establishing metastasis; however, they are not sufficient as this process is highly inefficient and most will fail to grow in target sites. Several CTC die during migration while others remain dormant for several years and very few grow into macrometastases. CTC have been well documented in the bloodstream of cancer patients; however, the clinical relevance of this detection is still the subject of controversies and their biology is poorly understood. Indeed, available markers fail to distinguish between subgroups of CTC, and several current methods lack sensitivity, specificity or reproducibility in CTC characterization and detection. The advent of more precise technologies is renewing the interest in CTC biology. We will review herein recent findings on CTC biology, on the role of host–tumor interactions in CTC shedding and implantation, available methods of CTC detection and future perspectives for the molecular characterization of the CTC subset(s) responsible for the development of metastasis. Ultimately, understanding CTC biology and host–tumor ‘complementarities’ will help define metastasis-related biomarkers providing formidable and tailored novel therapeutic targets.

Keywords::

• cancer therapy
• circulating tumor cell
• cytometry
• epithelial–mesenchymal transition
• invasion
• metastasis
• microarray
• PCR
• prognostic marker
• SNP

Financial & competing interests disclosure

This work was supported by the Canadian Institute of Health Research and the Matteo Buttino funds (Nada Jabado). Caroline Sollier is the recipient of a fellowship from the Cole Foundation and Karine Jacob a fellowship from Canadian Institutes of Health Research and the Montreal Children’s Hospital Research Institute. Nada Jabado is the recipient of a Chercheur Boursier Award from Fonds de la Recherche en Sante du Quebec. 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.

The authors would like to thank Janusz Rak for critical reading of this manuscript.

Notes

CTC: Circulating tumor cell.