The prognostic role of circulating tumor cells in colorectal cancer

ABSTRACT

Introduction: Metastasis is the main cause of cancer-associated death in colorectal cancer (CRC). The presence of circulating tumor cells (CTC) in the blood is associated with an increased risk of recurrence and poor prognosis. The clinical significance of CTCs as a novel biomarker has been extensively studied in the last decade. It has been shown that CTC detection applies to early cancer detection. The presence of CTCs is associated with metastatic spread and poor survival and is also useful as a marker for therapy response.

Areas covered: We summarize the role of CTC in CRC, their clinical significance, current methods for CTC detection and challenges as well as future perspectives of CTC research.

Expert commentary: The clinical significance of CTC in CRC patients is well established. Although insightful, the available marker-based approaches hampered our understanding of the CTCs and their biology, as such approaches do not take into account the heterogeneity of these cell populations. New technologies should expand the marker-based detection to multi biomarker-based approaches together with recent technological advances in microfluidics for single cell enrichment and analysis.

KEYWORDS:

• Colorectal cancer
• circulating tumor cells
• disseminated tumor cells
• cancer progression
• metastasis
• CTC detection

Article highlights

• EpCAM-based detection methods of CTCs do not take into account the presence of EpCAM negative CTCs and many other potential CTCs. A multi-marker-based isolation of CTCs or a label-free CTC detection method could help to overcome this problem.

• CTCs occur at a very low frequency in the blood (<1 to <50 in 7.5 mL blood of a metastatic cancer patient). Microfluidic-based label-free CTC enrichment might help researchers overcome the fact that CTCs are generally rare events, playing a vital role in CTC research.

• Methods that isolate CTCs based on their physical properties need to be further validated for clinical applications.

• There is a lack of information on the functional properties of the detected CTCs. Therefore, it is still challenging to identify CTCs with metastasis-initiating capabilities and optimize the design of effective therapies.

The current in vitro or xenotransplant models to identify clinically relevant CTCs are inefficient. Genetically engineered Mouse models or a combination of in vitro and in vivo assays, along with the new emerging CTC technologies, may help in efficiently identifying the clinically relevant CTCs.

Declaration of interest

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.