A groundbreaking advance in cancer diagnostics has emerged from a collaborative research endeavor involving the University Medical Center Hamburg-Eppendorf (UKE), CTCELLS, and the Department of New Biology at the Daegu Gyeongbuk Institute of Science & Technology (DGIST). Spearheaded by Professor Minseok Kim, this pioneering study introduces an innovative technology capable of automatically isolating both circulating tumor cells (CTCs) and circulating cancer-associated fibroblasts (cCAFs) from patient blood samples. This dual-capacity isolation marks a transformative step toward personalized and precise cancer diagnostics, offering unprecedented insights into the tumor microenvironment and promising to revolutionize how oncologists monitor and treat cancer patients.
The cornerstone of this research lies in a comparative analysis of three FDA-approved automated CTC isolation systems—each employing distinct methodologies: marker-based, size-based, and hemocyte extraction–based approaches. Testing these platforms on identical patient blood samples, the research team highlighted the superiority of the hemocyte extraction–based system branded as CTCeptor, a cutting-edge technology originally developed by DGIST and commercialized by CTCELLS. Notably, CTCeptor outperformed its counterparts in capturing heterogeneous tumor cell populations, overcoming intrinsic limitations faced by marker- and size-based methods that often miss subsets of cancer cells with variable marker expression or deformability.
Delving deeper into the performance metrics, the CTCeptor system demonstrated a remarkable capacity by detecting at least 15 times more circulating tumor cells in early-stage breast cancer patients compared to conventional technologies like CellSearch and Parsortix. Even more striking was the device’s ability to isolate circulating cancer-associated fibroblasts at an average frequency that far exceeded CTC detection rates—approximately tenfold higher. This finding underscores the significance of capturing cCAFs, which are key stromal components that modulate tumor progression, metastatic potential, and therapeutic resistance, yet have traditionally been neglected in liquid biopsy assays.
The implications of being able to analyze both tumor cells and their supportive microenvironment through a single blood draw are profound. Tumor-associated fibroblasts contribute significantly to the extracellular matrix remodeling, immune evasion, and maintenance of cancer stem cell niches, elements crucial for tumor growth and heterogeneity. The discovery of heterogeneity in CAF markers within blood-derived cells, as identified by the CTCeptor technology, represents a novel insight that can refine diagnostic precision and inform tailored treatment strategies that consider tumor-stromal interactions.
A pivotal aspect of this study involved rigorous testing across diverse cancer cell lines, including breast, lung, and ovarian cancers, as well as a breast cancer-derived CTC line. Across these various models, CTCeptor consistently demonstrated high recovery rates and robust performance irrespective of cell size—ranging from 13 to 17 micrometers—and EpCAM (epithelial cell adhesion molecule) expression levels. This is particularly noteworthy given that many traditional size- or marker-dependent technologies suffer from variable efficiency when confronted with tumor cell heterogeneity or cellular plasticity, such as changes in epithelial-mesenchymal transition states.
In contrast, size-based filtration methods illustrated inherent limitations. Such platforms can suffer from reduced capture efficiency due to physical deformability of certain tumor cells, which may allow them to escape capture pores or filters designed around fixed size thresholds. This intrinsic drawback highlights the potential for false negatives in clinical diagnostics, an issue ameliorated by the hemocyte extraction–based CTCeptor approach, which leverages a sophisticated cell isolation mechanism accounting for both physical and biological attributes of cancer cells and associated stromal components.
The innovation behind CTCeptor extends beyond mere capture efficiency. By simultaneously isolating tumor cells alongside cancer-associated fibroblasts from the same blood sample, this technology fosters a more comprehensive view of the tumor’s systemic presence and interaction with its microenvironment. This integrative liquid biopsy method holds significant promise for real-time monitoring of tumor evolution, therapeutic efficacy, and early detection of metastatic spread, potentially transforming clinical oncology practice by providing dynamic, individualized patient profiles.
Professor Minseok Kim emphasized the paradigm-shifting nature of this technology, articulating that despite a quarter-century of progress in liquid biopsy, prior efforts predominantly focused solely on tumor cells. The capability to concurrently analyze the tumor microenvironment’s cellular constituents offers unprecedented avenues for understanding tumor biology and pharmacodynamics. Such insights are critical for accelerating drug development pipelines and elevating the precision of personalized cancer therapies, thereby enhancing patient outcomes.
Funding for this landmark study was secured through prestigious grants from the National Research Foundation of Korea’s Mid-Career Project under the Individual Research Support Program, the European Research Council’s Advanced Investigator Grant, INJURMET, and the German Cancer Foundation (DKH) Priority Program on Translational Oncology. The multidisciplinary, international support reflects the global emphasis on advancing liquid biopsy technologies to meet urgent clinical needs.
The research findings have received notable recognition for their technical innovation and academic impact, culminating in publication as the cover story in Analytical Chemistry, a highly respected journal in the field of molecular and analytical sciences. This prominent placement underscores the study’s contribution to both fundamental knowledge and practical applications, positioning the CTCeptor technology as a frontrunner in the ongoing evolution of cancer diagnostics.
Looking forward, the ability to detect and characterize circulating cancer-associated fibroblasts alongside tumor cells may unlock deeper understanding of metastatic niches and mechanisms of chemoresistance. Expanding the repertoire of liquid biopsy analytes represents an exciting frontier that combines molecular biology, engineering, and clinical oncology, promising earlier interventions and dynamic treatment adjustments based on a patient’s unique tumor ecology.
In clinical practice, the integration of such advanced liquid biopsy tools could dramatically reduce the need for invasive tissue biopsies. Given the heterogeneity within tumors and across metastases, blood-based diagnostics offer a minimally invasive and repeatable method to capture the full spectrum of tumor biology over time, ultimately facilitating precision medicine approaches that adapt to tumor adaptation and progression.
Furthermore, the CTCeptor platform’s adaptability across multiple cancer types beyond breast cancer, including lung and ovarian malignancies, highlights its potential as a universal liquid biopsy tool. This versatility broadens its clinical utility, enabling oncologists to monitor various cancers with a single, robust diagnostic platform capable of capturing critical cellular players involved in different tumor microenvironments.
In conclusion, this pioneering research spearheaded by DGIST and collaborators represents a watershed moment in liquid biopsy technology. By simultaneously isolating circulating tumor cells and cancer-associated fibroblasts with unprecedented sensitivity and specificity, the CTCeptor platform enhances the resolution at which cancer can be monitored non-invasively. This technological breakthrough not only advances early diagnosis and treatment response assessment but also paves the way for novel therapeutic strategies that target both tumor cells and their supporting stroma, heralding a new era of personalized oncology.
Article Title: Robust Automated Separation of Circulating Tumor Cells and Cancer-Associated Fibroblasts for Enhanced Liquid Biopsy in Breast Cancer
Web References: https://doi.org/10.1021/acs.analchem.5c02154
Keywords
Tumor cells, Circulating tumor cells (CTCs), Cancer-associated fibroblasts (cCAFs), Liquid biopsy, Tumor microenvironment, Breast cancer diagnostics, Cell isolation technology, Precision medicine, Hemocyte extraction, Cancer heterogeneity, Early cancer detection, Personalized oncology
