Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer is one of the most frequent malignant tumors worldwide and the spread of tumor cells through the blood circulation followed by the colonization of distant organs (“metastases”) is the main cause of cancer-related death. The blood is, therefore, an important fluid that can be explored for diagnostic purposes. Liquid biopsy is a new diagnostic concept defined as the analysis of circulating tumor cells or cellular products such as cell-free DNA in the blood or other body fluids of cancer patients. In this review, we summarize and discuss the latest findings using circulating tumor cells and cell-free DNA derived from tumor lesions in the blood of patients with colorectal cancer. Clinical applications include early detection of cancer, identification of patients with a high risk for disease progression after curative surgery, monitoring for disease progression in the context of cancer therapies, and discovery of mechanisms of resistance to therapy. ABSTRACT: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. It is a heterogeneous tumor with a wide genomic instability, leading to tumor recurrence, distant metastasis, and therapy resistance. Therefore, adjunct non-invasive tools are urgently needed to help the current classical staging systems for more accurate prognostication and guiding personalized therapy. In recent decades, there has been an increasing interest in the diagnostic, prognostic, and predictive value of circulating cancer-derived material in CRC. Liquid biopsies provide direct non-invasive access to tumor material, which is shed into the circulation; this enables the analysis of circulating tumor cells (CTC) and genomic components such as circulating free DNA (cfDNA), which could provide the key for personalized therapy. Liquid biopsy (LB) allows for the identification of patients with a high risk for disease progression after curative surgery, as well as longitudinal monitoring for disease progression and therapy response. Here, we will review the most recent studies on CRC, demonstrating the clinical potential and utility of CTCs and ctDNA. We will discuss some of the advantages and limitations of LBs and the future perspectives in the field of CRC management.