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In the future, it is likely that ctDNA and CTCs will have complementary roles as cancer biomarkers although separate approaches may have distinct advantages in specificclinicalcontexts. ctDNA analysis is appealing due to the ease with which plasma can be collected and analyzed without the prior need to enrich and isolate a rare population of cells. For this reason, ctDNA analysis is likely to be the preferred option for genotyping and monitoring treatment response. The analysis of ctDNA can be applied as a high-throughput strategy for the assessment of clinical samples, but is limited to the analysis of point mutations, structural rearrangements, copy number aberrations and changes in DNA methylation. In contrast, the analysis of CTCs provides the unique opportunity to study the whole cell, allowing DNA, RNA and protein-based molecular profiling, and the opportunity for functional studies to guide personalized treatment selection. Although the analysis of both ctDNA and CTCs pose several technical challenges, ongoing improvements are expected over coming years, and both approaches hold great promise as biomarkers in various facets of cancer management. Technological advances might allow in the future, the use of a liquid biopsy (CTCs or ctDNA) for earlier cancer diagnosis or detection of disease relapse/progression. However, it is not known if earlier detection will lead to improved patient outcomes. This will become possible only if effective treatments are available to target early recurrences. Another open question is whether the liquid biopsy will complement analysis of primary tumor or metastases for tailoring treatment selection. Ongoing interventional clinical trials using CTC detection and characterization by CellSearch® will provide initial answers on the above question. Future research will be focused on optimizing and standardizing new technologies for both ctDNA and CTC analysis, demonstrating appropriate analytical and clinical validity as well as establishing the clinical utility of ctDNA and CTC testing through appropriately designed prospective clinical trials. |
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