Biofluid-Based Circulating Tumor Molecules as Diagnostic Tools for Use in Personalized Medicine

Abstract

Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA) and Extracellular Vesicles (ECVs) hold the key to understanding the biol. of tumor metastasis and provide a biomarker to noninvasively measure the evolution of tumor genotypes during treatment and disease progression. CTCs can be detected in blood from patients with metastatic and primary carcinomas. Over the past decade, the development of immune-magnetic platforms has permitted accurate enumeration of CTCs at extremely low frequencies. In several case reports, the presence of CTCs has been assocd. with shortened survival times. Circulating-mutant DNA in blood is believed to originate from apoptotic and necrotic cells of the primary tumor, which discharge their DNA early during tumorigenesis. It is conceivable that cell-free tumor-specific DNA could also be related to the rate of turnover of CTCs. Extracellular Vesicles (ECVs) are nano-sized vesicles released by all cells in vitro as well as in vivo. Their role has been implicated mainly in cell-cell communication, but also in disease biomarkers and more recently in gene delivery. They represent a snapshot of the cell status at the moment of release and carry bio-reactive macromols. such as nucleic acids, proteins, and lipids. Improvements in technologies to isolate purer CTCs, ECVs and ctDNAs will help in a better characterization and enable a broad range of clin. applications, including early detection of disease and the discovery of personalized biomarkers to predict treatment responses and disease progression. This review highlights the progress made in the development of noninvasive biomarkers using CTCs, ctDNA and ECVs. [on SciFinder(R)]