Assessment of Circulating Nucleic Acids in Cancer: From Current Status to Future Perspectives and Potential Clinical Applications.

Current approaches for cancer detection and characterization are based on radiological procedures coupled with tissue biopsies, despite relevant limitations in terms of overall accuracy and feasibility, including relevant patients' discomfort. Liquid biopsies enable the minimally invasive collection and analysis of circulating biomarkers released from cancer cells and stroma, representing therefore a promising candidate for the substitution or integration in the current standard of care. Despite the potential, the current clinical applications of liquid biopsies are limited to a few specific purposes. The lack of standardized procedures for the pre-analytical management of body fluids samples and the detection of circulating biomarkers is one of the main factors impacting the effective advancement in the applicability of liquid biopsies to clinical practice. The aim of this work, besides depicting current methods for samples collection, storage, quality check and biomarker extraction, is to review the current techniques aimed at analyzing one of the main circulating biomarkers assessed through liquid biopsy, namely cell-free nucleic acids, with particular regard to circulating tumor DNA (ctDNA). ctDNA current and potential applications are reviewed as well.