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Updated: May 3, 2026
Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment
Published on: May 14, 2019
Molecular analysis of circulating tumour cells-biology and biomarkers
Matthew G Krebs1, Robert L Metcalf1, Louise Carter1
1Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Abstract:
Growing evidence for intratumour heterogeneity informs us that single-site biopsies fall short of revealing the complete genomic landscape of a tumour. With an expanding repertoire of targeted agents entering the clinic, screening tumours for genomic aberrations is increasingly important, as is interrogating the tumours for resistance mechanisms upon disease progression. Multiple biopsies separated spatially and temporally are impractical, uncomfortable for the patient and not without risk. Here, we describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test-and readily amenable to serial sampling-have the potential to inform intratumour heterogeneity and tumour evolution, although it remains to be determined how useful this will be in the clinic. Technologies for detecting and isolating CTCs include the validated CellSearch(®) system, but other technologies are gaining prominence. We also discuss how recent CTC discoveries map to mechanisms of haematological spread, previously described in preclinical models, including evidence for epithelial-mesenchymal transition, collective cell migration and cells with tumour-initiating capacity within the circulation. Advances in single-cell molecular analysis are enhancing our ability to explore mechanisms of metastasis, and the combination of CTC and cell-free DNA assays are anticipated to provide invaluable blood-borne biomarkers for real-time patient monitoring and treatment stratification.
Insights
Circulating tumor cells (CTCs) from blood tests offer a less invasive way to understand tumor evolution and heterogeneity. Serial sampling of CTCs may aid in real-time monitoring and treatment decisions for cancer patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Intratumor heterogeneity highlights limitations of single-site biopsies for comprehensive tumor profiling.
- Targeted therapies and resistance mechanisms necessitate accurate genomic screening and monitoring.
- Multiple tumor biopsies are invasive, uncomfortable, and carry risks for patients.
Purpose of the Study:
- To explore the potential of circulating tumor cells (CTCs) as a minimally invasive tool for assessing tumor heterogeneity and evolution.
- To discuss current and emerging technologies for CTC detection and isolation.
- To examine the role of CTCs in understanding mechanisms of cancer metastasis and hematological spread.
Main Methods:
- Review of technologies for detecting and isolating circulating tumor cells (CTCs), including the CellSearch® system and emerging platforms.
- Analysis of recent discoveries linking CTC characteristics to mechanisms of hematological spread, such as epithelial-mesenchymal transition and collective cell migration.
- Discussion of advances in single-cell molecular analysis and the integration of CTCs with cell-free DNA (cfDNA) assays.
Main Results:
- Circulating tumor cells (CTCs) captured via blood tests offer a promising, minimally invasive approach for serial sampling.
- CTCs can provide insights into intratumor heterogeneity and tumor evolution, complementing traditional biopsy methods.
- Emerging CTC technologies and their application in understanding metastasis and guiding treatment stratification are discussed.
Conclusions:
- Circulating tumor cells (CTCs) hold significant potential for real-time monitoring of tumor evolution and heterogeneity.
- The combination of CTC and cell-free DNA (cfDNA) assays is anticipated to yield powerful blood-borne biomarkers for personalized cancer care.
- Further research is needed to fully establish the clinical utility of CTCs in patient management and treatment stratification.
