Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine

Abstract

Current trajectory of clinical care is heading in the direction of personalized medicine. In an ideal scenario, clinicians can obtain extensive diagnostic and prognostic information via minimally-invasive assays. Information available in the peripheral blood has the potential to bring us closer to this goal. In this review we highlight the contributions of circulating tumor cells and circulating tumor DNA and RNA (ctDNA/ctRNA) towards cancer therapeutic field. We discuss clinical relevance, summarize available and upcoming technologies, and hypothesize how future care could be impacted by a combined study.

Keywords: cell free DNA; cell free RNA; circulating tumor DNA; circulating tumor RNA; circulating tumor cells; exosomes.

© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Multitude of factors secreted in the circulatory system with the sustained growth of a primary/localized tumor. These can include invasive cells that become CTCs and exosomal and ctDNA/RNA. The CTCs can attach at distant sites and form secondary lesions. A liquid biopsy, obtained from a simple blood draw may help predict such an event though changes in CTCs and ctDNA levels and their genetic and epigenetic constitution.

Figure 2.

CTC isolation methods and an inventory of circulating DNA/RNA components. A blood sample can be processed for CTC isolation using multiple techniques as illustrated. The plasma portion of the sample also contained various types of genetic materials such as circulating tumor mirco RNA, ctDNA, and lncRNA. These molecules may or may not be encased in an exosomal vescicle.

Figure 3.

A liquid biopsy contains wealth of information relevant to determining tumor status, metastatic potential, and likelihood of relapse. Some of the contributing factors to making such an assessment include CTC counts, CTC genetic profile and protein expression, levels of ctDNA/RNA and the presence or absence of known mutations or epigenetic signatures. A thorough analysis of liquid biopsies from cancer patients screening for these factors can reveal essential information for personalized care.