What are Circulating Tumor Cells or CTCs?
Circulating tumor cells are malignant cells that are shed from the primary and/or metastatic solid tumors and then infiltrate into the vascular and lymphatic systems. They play a fundamental role in the metastatic process of non-hematological cancers.
Being able to detect CTCs in the bloodstream can be extremely helpful for the diagnosis of cancer at early stages. Furthermore, the analysis of these cells can enable the identification of their genetic characteristics and the expression of specific surface markers. This would allow to monitor the evolution of the disease, significantly improving the understanding of each patient’s cancer, and providing invaluable information for the personalization of their treatments.
The heterogeneity and the extremely low concentration of these cells in regard to the cellular components of blood, about 1-10 CTCs per 10^9 blood cells, has made their capture extremely challenging so far.
Clinical applications of the isolation
and analysis of CTCs
The successful isolation and analysis of CTCs from blood will unlock the following clinical applications:
CTCs have the potential to be used as a biomarker for recurrence and early cancer detection.
Measuring CTCs levels in patients and monitoring their changes over time is associated with the effectiveness of the administered therapies.
The phenotypic and genotypic analysis of CTCs enable the continuous assessment of mutations that confer therapeutic sensitivity or resistance to targeted therapies, providing information that is of paramount importance for cancer treatment personalization.
CTCs may be used as a prognostic indicator of disease progression and overall survival in patients.
Single cell analysis of CTCs captured may enable the study of their heterogeneity in cancer patients and may improve the understanding of the biology of the metastatic process potentially leading to the development of new therapies.
At Delee, we have created the CytoCatch™, a highly sensitive automated benchtop device for the rapid isolation and efficient analysis of circulating tumor cells (CTCs) from blood samples. Our technology is comprised of a fully automated sample processing unit and an imaging system which, along with the embedded artificial intelligence it possesses, inhibits human mistakes due to manual sample handling, and suppresses subjective interpretation errors.
The CytoCatch™ enables the early detection of cancer, the continuous monitoring of the disease’s evolution and the effectiveness of therapies that are being administered.
CytoCatch™: taking liquid biopsies from the laboratory to clinical practice
The 'liquid biopsy' approach based on the capture, enumeration, and characterization of CTCs is rapidly becoming a valuable tool in translational medicine. To enable a fast and easy adoption in the clinical setting, CytoCatch™ has fully automated the isolation, preparation, and analysis of the captured CTCs to prevent human error and cell loss due to the manual steps that must be performed.
Once the sample is processed, the tumoral cells are dyed with fluorescent antibodies to discriminate between the tumoral cells and the cellular components of blood. Later, an imaging system which possesses an artificial intelligence algorithm, automatically perform a classification of the fluorescent events and enumeration of the captured CTCs, based on their morphology and the expression of specific antigens.
All these procedures have been optimized in order to enable physicians to focus on the clinical relevant aspects of the disease, instead of the technology.
A powerful tool to unleash the CTCs clinical potential
Cytocatch™ has been developed as a technology that could be easily taken to the clinical practice while being an extremely valuable research tool.
Captured CTCs are compatible with a broad range of downstream analysis
Enables the identification of predictive and therapeutic markers expressed in CTCs, such as AR-V7, HER-2, EGFR, PD-L1, among others.
Enables in vitro assessment of drug susceptibility/resistance on patients’ CTCs.
Detection of genetic aberrations, such as chromosomal amplifications, deletions, and translocations that serve as targets for the development of new therapeutic regimes.
Genotypic analysis of CTCs allows the continuous assessment of mutations that confer therapeutic sensitivity or resistance to targeted therapies, providing information that is of paramount importance for cancer treatment personalization. Sequencing of captured CTCs can be performed by conventional methods or by NGS.
Gene expression analysis
Target cDNA molecules can be amplified using fluorescent probes to perform gene expression analysis using techniques, such as DNA microarrays, RT-PCR, qRT-PCR, and digital PCR.
CytoCatch™ is capable of capturing CTCs subtypes that no longer express epithelial antigens
Most CTCs technologies, are based on sample enrichment methods that depend on specific antigen-antibody interactions. However, a fundamental problem of these approaches is the lack of a universal surface marker that is consistently expressed by CTCs. Typically these technologies, use EpCAM (epithelial cell adhesion molecule) antibodies to selectively trap cancer cells to a functionalized substrate. Nonetheless, CTCs intravasate into the bloodstream by undergoing a process known as the epithelial-mesenchymal transition (EMT), in which their epithelial phenotype is downregulated, including the expression of EpCAM antigens. This fact limits the capture of CTCs subpopulations with diminished expression of this specific surface marker, thereby losing valuable information. The principle of separation used by the CytoCatch is based on the differences in size and deformability between blood cells and CTCs, enabling the isolation of CTCs irrespective of the level of proteins expressed in their membranes, and allowing us to capture cells that other technologies can’t.