[Liquid biopsy in colorectal cancer : An overview of ctDNA analysis in tumour diagnostics]

In current routine diagnostics, the gold standard to determine the genomic profile of colorectal cancers (CRCs) is using biopsy or surgically resected tissues. However, such a tissue sample cannot represent the entire tumour heterogeneity, because it only shows a local and temporal snapshot. As a complement to tumour tissue genotyping, liquid biopsies enable minimally invasive detection of all potential tumour-specific mutations and their dynamic changes for molecular profiling. Furthermore, they can be repeated in certain intervals for monitoring response to treatment, occurrence of drug resistance and detection of relapse. This review focusses on analyzing circulating cell-free tumour DNA (ctDNA), which is mostly released from apoptotic or necrotic tumour cells into the bloodstream or by active secretion of circulating tumour cells (CTCs). Nevertheless, there are some challenges in analyzing ctDNA. First, ctDNA represents only a small fraction of total circulating DNA, because there is an enormous wild-type background of cell-free DNA (cfDNA) released by healthy cells. Second, ctDNA is highly fragmented and the amount of ctDNA in the blood is very low. In this review, we discuss the potential, fields of application as well as challenges and limitations of liquid biopsy approaches. In more detail, we discuss the possibility of using liquid biopsies as a future application for molecular characterization of CRCs, particularly for monitoring CRC patients during anti-EGFR therapy to detect resistance mutations (e.g. KRAS mutations) or further therapy-relevant mutations. In addition, we investigate whether blood-based molecular profiling is a reliable addition to routine diagnostic approaches of tissue-based molecular characterization.