Clinical Applications of Circulating Tumor DNA, Circulating Tumor Cells, and Exosomes as Liquid Biopsy-Based Tumor Biomarkers

Along with improved knowledge of cancer biology and biotechnical progress, the diagnostic approaches have evolved from tissue biopsies to liquid biopsies. As they provide a minimally invasive tumor detection, liquid biopsies allow early diagnosis and serial assessments of tumor progression. Discovery and use of circulating tumor markers circulating tumor DNA (ctDNA), circulating tumor cells (CTC), and exosomes have largely expanded the possibility of early diagnosis of cancer, patient stratification, as well as developing a personalized treatment. Based on these circulomes, liquid biopsies can be developed, but each type of liquid biopsies has its own merits and limitations. While ctDNA-based methods represent the most advanced techniques, sensitivity improvement is expected given the rarity of ctDNA in circulation. As intact cancer cells, CTC provide information on cancer cells. However, current CTC capturing procedures are still lack of efficiency. Exosomes are abundant, but they are highly heterogeneous and there is a lack of specific markers for identification. Future efforts are needed to improve operational parameters and clinical performance of each method. Prior to a broad use in clinical settings, it is crucial to standardize the procedure for the specific liquid biopsy method and validate the test with adequate specificity and sensitivity for clinical applications.