Design and technological approaches for the detection and isolation of Circulating Tumor Cells

Metastasis, the process by which tumor cells spread throughout the body via the bloodstream, is the leading cause of cancer-related mortality¹. Circulating tumor cells (CTCs) are shed tumor cells that have entered the bloodstream from the primary tumor. The functional and molecular properties of CTCs may provide in-depth knowledge of cancers with a high mortality rate. Given the extremely low quantity of CTCs in the blood of cancer patients, it remains a substantial problem to consistently isolate CTCs from the innumerable blood cells and, in particular, to develop technologies that can efficiently detect live CTCs for in-depth analysis. The exponential growth of CTC-related technologies during the past two years are analyzed herein. A conceptual roadmap to CTC-related technologies is provided, with a particular emphasis on the most creative techniques employing nanomaterials or unique microfluidic chips. In general, CTCs technologies apply three core methods²: i) separation and enrichment; ii) detection and characterisation; and iii) release. The first method requires a specific interface between CTCs and materials, either through physical processes or antibody-antigen interaction. The second method, recognizing CTCs, involves a number of technologies (i.e. fluorescence spectrophotometry/microscopy; flow cytometry). In the final strategy, CTCs are employed mostly for downstream analysis (i.e. genomes, -omics, CTCs culture). In brief, emerging technologies for the detection of CTCs have profoundly contributed to cancer monitoring, efficacy evaluation and the design of targeted cancer treatment approaches, and will become an essential component of cancer management in the future.

Acknowledgments: This research was supported by the Norte Portugal Regional Coordination and Development Commission (CCDR-N) through the NORTE-01-0145-FEDER-000055 project and by the European Commission (EU-EC) through the ONCOSCREEN project (101097036);

References:

[1] Ring, A. et al.,  Nat. Rev. Cancer. 23, 95-111 (2023).

[2] Lin, D. et al., Curr. Signal Transduct. Ther. 6, 404. (2021).