Circulating Tumor Cells and Cell-free Nucleic Acids as Biomarkers in Colorectal Cancer

Colorectal cancer (CRC) is currently the second most prevalent cancer diagnosed in women and thethird most common kind of cancer in men. Despite tremendous efforts and advancements in diagnostic approachesand treatment options, the mortality rate of CRC accounts for around one million each year globally.The five-year survival rate of CRC is reported to be approximately 14 percent for patients diagnosed at an advancedstage. Due to its significant associated mortality and morbidity, diagnostic tools to identify the diseaseat its early stages are urgently required. Early diagnosis may lead to better outcomes. The gold standard approachfor CRC diagnosis is colonoscopy with biopsy. However, it is an invasive process with a risk of complicationsand discomfort for the patient. Moreover, it is usually performed in symptomatic or high-risk individualsand therefore, asymptomatic patients might be missed. Thus, alternative non-invasive diagnostic techniquesare required to improve CRC outcomes. The new era of personalized medicine is identifying novel biomarkersassociated with overall survival and clinical outcomes. Recently, liquid biopsy, a minimally invasive analysis ofbody fluid biomarkers, has gained attention for diagnosis, evaluation of prognosis, and follow-up of patientswith CRC. Several previous studies have demonstrated that this novel approach allows for better understandingof CRC tumor biology and leads to an improvement in clinical outcomes. Here, we explain the enrichmentand detection methods of circulating biomarkers, including CTCs, ctDNA, miRNA, lncRNA, and circRNA.Furthermore, we provide an overview on their clinical potential as diagnostic, prognostic, and predictivebiomarkers for CRC.