Advanced technologies for studying circulating tumor cells at the protein level

Abstract

Metastasis is the main cause of cancer death. As the tumor progresses, cells from the primary tumor site are shed into the bloodstream as circulating tumor cells (CTCs). Eventually, these cells colonize other organs and form distant metastases. It is therefore imperative that we gain a better understanding of the biological characteristics of CTCs for development of novel treatment modalities to minimize metastasis-associated cancer deaths. In recent years, rapid developments in technologies for the study of CTCs have taken place. We now have a variety of tools for the isolation and examination of CTCs which were not available before. This review introduces some commonly used protein markers in CTC investigations and summarizes a few advanced technologies which have been successfully applied for studying CTC biology at the protein level.

Keywords::

• CellSearch
• circulating tumor cells
• CTC-chip
• EPISPOT
• immunomagnetic bead
• proteomic

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Circulating tumor cells (CTCs) may provide real-time information regarding tumor characteristics to help make clinical decisions during patient prognostication, treatment planning and disease monitoring.

• • A wide variety of tools are now available for studying CTCs. It is now possible to identify CTCs by differential marker expression, density, size and viability. These advances have facilitated our understanding of the processes leading to the development of metastases.

• • However, challenges still lie ahead. Downregulation of epithelial markers in CTCs by epithelial–mesenchymal transition hinders our ability to capture CTCs with high efficiency. The addition of antibodies targeting mesenchymal markers may help in alleviating this problem.

• • Although there has been immense progress in the development of tools for investigating CTCs, currently available techniques are still limited and suffer from problems such as low throughput or suboptimal sensitivities and specificities.

• • Most of the techniques have not been validated in large-scale clinical trials.

• • A deeper understanding of the underlying biology of CTCs would definitely aid our quest to develop better therapeutic options for cancer treatment.

Notes