The liquid biopsy in the management of colorectal cancer patients: Current applications and future scenarios

The term liquid biopsy refers to the analysis of biomarkers in any body fluid, including blood, urine and cerebrospinal fluid. In cancer, liquid biopsy testing allows the analysis of tumor-derived DNA, RNA, miRNA and proteins that can be either cell-free or contained in circulating tumor cells (CTC), extracellular vesicles (EVs) or platelets. A number of studies suggest that liquid biopsy testing could have a relevant role in the management of colorectal cancer (CRC) patients at different stages of the disease. Analysis of cell-free DNA (cfDNA), CTC and/or miRNA can provide relevant information for the early diagnosis of CRC and the identification of minimal residual disease and, more generally, the evaluation of the risk of recurrence in early CRC patients. In addition, liquid biopsy testing might allow the assessment of prognostic and predictive biomarkers in metastatic CRC patients, and the monitoring of the response to treatment and of the clonal evolution of the disease. While a number of elegant studies have shown the potential of liquid biopsy in CRC, the possibility to use this approach in the daily clinical practice is still limited. The use of non-standardized methods, the small cohorts of patients analyzed, the lack of demonstration of a clear clinical benefit are the main limitations of the studies with liquid biopsy in CRC reported up to now. The potential of this approach and the steps that need still to be taken to translate these preliminary findings in the clinic are discussed in this review.