Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities

Abstract

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization.

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

“…Identifying molecular defects involved in cancer progression and drug resistance is critical to improving cancer diagnosis and treatment. [110] Because of the rarity of CTCs in blood, the establishment of CTC cell lines has been challenging. Nowadays, researchers have successfully built CTCs cell lines, [111][112][113] which is a major breakthrough in CTCs research.…”

Fast, Reusable, Cell Uniformly Distributed Membrane Filtration Device for Separation of Circulating Tumor Cells

“…However, this has always been challenging since CTCs are rare and fragile in peripheral blood . Nowadays, methods using the biological or physical properties of CTCs and methods combined to detect or capture CTCs are gradually emerging; however, there is still a long way to go to reach extensive clinical routine use. The immunocapture methods show good specificity but deeply rely on the expression level of cell surface biomarkers .…”

Electric field-assisted MnO2 nanomaterials for rapid capture and in situ delivery of circulating tumour cells

“…Circulating tumour cells (CTCs) are formed by the spread of cancer cells in the primary tumour or metastatic tumour into the peripheral blood circulation system, and are of great value in the early diagnosis of cancer, monitoring of metastasis, evaluation of curative effect [5][6][7] and the revelation of aggressive potential and gene mutations. [8][9][10] More critically, CTC detection has outstanding advantages such as non-invasiveness, low sample consumption, and real-time detection.…”

“…[8][9][10] More critically, CTC detection has outstanding advantages such as non-invasiveness, low sample consumption, and real-time detection. 5 Compared with the samples required by current drug screening technologies (cell spheroids, organoids, etc. ), CTCs derived from patient tumour tissues can not only avoid long-term secondary culture, but also have a higher similarity to tumour tissues.…”