Circulating Cell-Free DNA and Colorectal Cancer: A Systematic Review

Abstract

There is a strong demand for the identification of new biomarkers in colorectal cancer (CRC) diagnosis. Among all liquid biopsy analysts, cell-free circulating DNA (cfDNA) is probably the most promising tool with respect to the identification of minimal residual diseases, assessment of treatment response and prognosis, and identification of resistance mechanisms. Circulating cell-free tumor DNA (ctDNA) maintains the same genomic signatures that are present in the matching tumor tissue allowing for the quantitative and qualitative evaluation of mutation burdens in body fluids. Thus, ctDNA-based research represents a non-invasive method for cancer detection. Among the numerous possible applications, the diagnostic, predictive, and/or prognostic utility of ctDNA in CRC has attracted intense research during the last few years. In the present review, we will describe the different aspects related to cfDNA research and evidence from studies supporting its potential use in CRC diagnoses and the improvement of therapy efficacy. We believe that ctDNA-based research should be considered as key towards the introduction of personalized medicine and patient benefits.

Keywords: cell-free DNA; colorectal cancer; liquid biopsy.

Figure 1

A liquid biopsy for solid tumors. A literature scan of the last few years revealed an enormous increase in liquid biopsy-based analyses [20].

Figure 2

A liquid biopsy to monitor the therapy response and resistance. A hypothetical scenario of the developing chemotherapy resistance of colorectal cancer patients: first-line therapy is based on the primary tumor and relevant changes in the metastasis might be overlooked, therefore, leading to primary resistance. After switching to second-line therapy, secondary resistance may arise. Genetic changes of the resistant clones can be monitor using liquid biopsy and, therefore, the resistance mechanism might be recognized before disease progression (adapted from Heitzer et al. [12]).