The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells

Abstract

Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood, which represents a precious source of biological material derived from both primary and metastatic tumors, has been named a ‘liquid biopsy’. While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient’s individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system. The analysis of viable CTCs at DNA, RNA and protein levels, as well as their expansion in vitro, may allow deep investigation of the features of metastases-initiating cells.

Keywords:

• cancer stem cells
• circulating tumor cells
• colorectal cancer
• epithelial–mesenchymal transition
• liquid biopsy
• targeted therapy

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

• Liquid biopsy might provide ‘real time’ information on disease burden, shedding light on tumor evolution over time and on its heterogeneity.

• In colorectal cancer (CRC), the enumeration of circulating tumor cells (CTCs) for prognostic purpose needs to be explored in non-metastatic setting, specifically high risk stage II CRC patients, where the role of adjuvant therapy is debated.

• In metastatic setting a comparison between the ‘all-RAS’ mutational status of primary tumor and that of liquid biopsy is potentially useful to follow cancer evolution as a ‘moving target’.

• The finding of CD44v6 positive CTCs in bloodstream of metastatic CRC patients supports the hypothesis that the CTC population contains CSCs, and lightens the possibility of an easily reproducible liquid biopsy to develop new CCSC-targeted drugs in CRC.

• CTC clusters are described to travel into the bloodstream ‘protected’ by platelets, which are believed to be powerful activators of epithelial–mesenchymal transition in CTCs through TGF-β and PDGF pathways.

• The analysis of circulating clusters in metastatic CRC through liquid biopsies might allow us to explore a new role of aspirin and anti-platelet drugs as modulators of epithelial–mesenchymal transition features in CTCs.

Notes