Technologies for circulating tumor cell separation from whole blood

Abstract

The importance of early cancer diagnosis and improved cancer therapy has been clear for years and has initiated worldwide research towards new possibilities in the care strategy of patients with cancer using technological innovations. One of the key research fields involves the separation and detection of circulating tumor cells (CTC) because of their suggested important role in early cancer diagnosis and prognosis, namely, providing easy access by a liquid biopsy from blood to identify metastatic cells before clinically detectable metastasis occurs and to study the molecular and genetic profile of these metastatic cells. Provided the opportunity to further progress the development of technology for treating cancer, several CTC technologies have been proposed in recent years by various research groups and companies. Despite their potential role in cancer healthcare, CTC methods are currently mainly used for research purposes, and only a few methods have been accepted for clinical application because of the difficulties caused by CTC heterogeneity, CTC separation from the blood, and a lack of thorough clinical validation. Therefore, the standardization and clinical application of various developed CTC technologies remain important subsequent necessary steps. Because of their suggested future clinical benefits, we focus on describing technologies using whole blood samples without any pretreatment and discuss their advantages, use, and significance. Technologies using whole blood samples utilize size-based, immunoaffinity-based, and density-based methods or combinations of these methods as well as positive and negative enrichment during separation. Although current CTC technologies have not been truly implemented yet, they possess high potential as future clinical diagnostic techniques for the individualized therapy of patients with cancer. Thus, a detailed discussion of the clinical suitability of these new advanced technologies could help prepare clinicians for the future and can be a foundation for technologies that would be used to eliminate CTCs in vivo.

Single Cell Transcriptome in Colorectal Cancer—Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells

“…At present, various technologies are developed for CTCs isolation, however, they are mainly used for research purposes rather than clinical applications (Bankó et al, 2019). Among the obstacles are the presence of ITH (Levitin et al, 2018;Lim et al, 2019), limited knowledge on CTCs mechanism of action in cancer progression (shedding from the primary/metastasis tumor, survival in bloodstream, avoidance of apoptosis, colonization potentials and settlement in distant organs), the rarity of CTCs (0 to 10 CTCs/ml whole blood in 30% to 50% mCRC patients) (Zieglschmid et al, 2005), various sizes of CTCs and the lack of clinical validation (Millner et al, 2013;Rejniak, 2016;Kowalik et al, 2017;Bankó et al, 2019). In addition, there are only a few studies relating to CTCs pharmacogenomics and underlying survival mechanisms (Wang et al, 2018) as well as the cell-cell interactions in CRC microenvironment (Krog and Henry, 2018), and majority of them are based on experimental and theoretical extrapolations (Burz et al, 2018).…”

Non-Invasive Biomarkers for Early Detection of Breast Cancer

“…CTCs are rare and there is as few as one CTC per billion normal blood cells [ 78 ]. Many technologies have been assessed for enumeration and analyses of CTCs based on physical characteristics, immunomagnetic separation, and immunofluorescence/enzyme-linked immunosorbent assays, as well as reverse transcription polymerase chain reaction (RT-PCR) assays [ 78 , 79 , 80 , 81 ]. Among the many CTC technologies, CellSearch ® (Janssen Diagnostics, Raritan, NJ, USA) and AdnaTest ® (AdnaGen AG, Langenhagen, Germany) have been widely studied in clinical trials.…”

Gauging the Impact of Cancer Treatment Modalities on Circulating Tumor Cells (CTCs)

“…Other methods of CTC isolation are label-free techniques utilizing filtration and fluid dynamics based on tumor cells size and deformability and not on epithelial marker detection. Different CTC collection and isolation techniques have been extensively reviewed, and thus will not be discussed here (reviewed in [48][49][50][51][52][53][54]). However, it is important to recognize that all studies discussed in this review did not use the same CTC isolation method and any incompatible results may be attributed to different CTC isolation approaches, and a component of variability is likely due to differences in detection method.…”