Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer (CRC) is a disease that usually shows no evident clinical symptoms in the early stages, often leading to late diagnosis. Over the past few years, a new approach based on liquid biopsy has gained far-reaching applications in less-invasive CRC diagnosis and management, allowing for the use of extracellular nucleic acids as promising biomarkers to detect CRC at an early stage and monitor disease recurrence. That is why an up-to-date review and discussion of in-depth liquid biopsy-derived DNA and RNA biomarkers is essential. We hereby offer an overview of known predisposing genetic factors for developing sporadic and hereditary CRC, and an extensive repertoire of available extracellular DNA/RNA molecules with their potential clinical applications and shortcomings. Our review may be of value to experts dealing with CRC at the molecular level as well as to clinical professionals aiming for a better understanding of state-of-the-art techniques in CRC diagnosis and management. ABSTRACT: Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management.