CTCs and liquid biopsy: key technology for precision oncology
Liquid biopsy has become a key tool in translational oncology. While cfDNA analysis is already widely used, circulating tumor cells (CTCs) provide a more complex and informative sample. These cells are intact and viable, allowing real-time genomic, transcriptomic, proteomic, and functional analysis.
However, their low frequency in peripheral blood (1–10 cells per mL) remains a major challenge. Therefore, efficient isolation technologies are required to preserve both structural and molecular integrity.
The Parsortix® system addresses this need through an epitope-independent microfluidic approach. Specifically, it captures cells based on physical properties, enabling viable recovery and downstream analysis.
From a biological perspective, CTCs offer several advantages over ctDNA. First, they provide intact tumor cells. In addition, they enable single-cell analysis. Moreover, they allow simultaneous evaluation of DNA, RNA, and proteins. As a result, they support detailed clonal and functional characterization.
International consensus 2025: clinical consolidation and functional redefinition
In 2025, an international panel of experts published a structured consensus in European Journal of Cancer on the clinical integration of CTCs in solid tumors.
The conclusions establish that:
• There is sufficient evidence for the clinical use of CTCs in metastatic disease, particularly in breast and prostate cancer.
• Enumeration constitutes a validated prognostic biomarker in this context.
• The next stage of clinical development should focus on phenotypic and molecular characterization.
• Integration with ctDNA represents a strategic axis for field advancement.
• Antigen-independent technologies gain relevance within this transition.
This consensus consolidates the clinical validity of CTCs in advanced disease and establishes a conceptual framework oriented toward molecular and functional characterization as the next evolutionary step.
Microfluidic capture based on size and deformability
The technological architecture of Parsortix aligns with this approach by prioritizing the recovery of intact and analytically exploitable cells.
Parsortix is based on separation by size and deformability. The microfluidic cassette incorporates a progressive reduction of the channel until reaching a “critical gap,” where hematologic cells pass through the system while tumor cells—generally larger and less deformable—are retained.
This approach is particularly relevant in the context of tumor heterogeneity.
Tumor heterogeneity and epithelial–mesenchymal transition (EMT)
CTCs do not constitute a uniform population. During processes such as epithelial–mesenchymal transition (EMT), they may lose classical epithelial markers and acquire mesenchymal or hybrid phenotypes.
Epitope-independent capture enables the recovery of:
• epithelial CTCs
• mesenchymal CTCs
• intermediate EMT states
• tumor cell clusters
Thus, preserving the phenotypic and potentially functional diversity of the circulating population.
From prognostic biomarker to therapeutic stratification tool
The international consensus highlights a conceptual transition:
• In current practice, CTC enumeration has validated prognostic utility in metastatic disease.
• In future development, molecular and proteomic characterization will be critical for response prediction and therapy selection.
• The evaluation of biomarkers such as HER2, TROP2, PD-L1, PSMA, or c-MET in CTCs is identified as a priority line for advancing toward personalized medicine models.
From a biological perspective, CTCs offer differential advantages over ctDNA:
• cellular tumor material
• single-cell analysis capability
• simultaneous DNA, RNA, and protein evaluation
• clonal and subclonal characterization
• potential for functional studies
By enabling the recovery of viable cells, Parsortix facilitates the transition from quantitative detection to integrated multi-omic characterization.
Biological complementarity with ctDNA
The consensus emphasizes that CTCs and ctDNA represent biologically complementary analytes.
ctDNA reflects DNA fragments released into the bloodstream, mainly derived from tumor apoptosis or necrosis.
In contrast, CTCs are intact cells with preserved architecture and full biological context.
The integration of both analytes can:
• increase sensitivity in minimal residual disease (MRD)
• refine prognostic models
• expand the proportion of evaluable patients
• provide non-overlapping biological information
Parsortix enables this multimodal model through:
• plasma separation for cfDNA analysis
• subsequent cellular capture within the same workflow
• downstream molecular and proteomic analysis
Early disease and MRD monitoring
In non-metastatic disease, the consensus recognizes that clinical utility is not yet established, although strong biological validity exists, especially in early breast cancer.
Main limitations include:
• low CTC frequency
• pre-analytical and analytical variability
• need for greater sensitivity and reproducibility
The development of prospective multicenter studies and methodological harmonization will be key to translating biological validity into demonstrated clinical utility.
Alignment with strategic priorities in the field
The consensus defines the following priorities:
• standardization of pre-analytical and analytical protocols
• structured integration with ctDNA
• characterization of key therapeutic biomarkers
• generation of robust clinical evidence
• design of biomarker-driven prospective trials
In this context, cell capture represents only the initial phase of the analytical process. The ultimate goal is to obtain biologically relevant information with functional and translational value.
In this scenario, Parsortix is not merely a cell enrichment technology, but an analytical platform that integrates capture, viability, and multi-omic characterization within a single experimental workflow, expanding the biological scope of liquid biopsy.
