**1. Introduction**

Ongoing research in oncology aims to generate patient-directed treatment options, targeting each individual's specific cancer molecular profile with therapies most likely to initiate and maintain an effective anti-tumour response [1]. Currently, molecular profiling in colorectal cancer (CRC) relies on direct biopsy of tumour tissue. However, tissue biopsy presents a number of procedural and biological challenges. Firstly, it is an inherently invasive procedure, making recurrent sampling difficult. Secondly, results may be affected by bias owing to tumoural heterogeneity. Tumours are affected by factors such as genomic instability, the surrounding tissue microenvironment and therapeutic effects [2]. These influences create dynamic molecular selection and evolution, resulting in spacial and temporal heterogeneity, which cannot be represented by a single site tissue biopsy, particularly in the case of metastatic disease [3].

Recognition of these limitations has prompted an interest in non-invasive circulating tumour-specific biomarkers. The concept of 'liquid biopsy' originally described the detection and analysis of circulating tumour cells (CTC) in blood, with reference to tissue biopsy. More recently, it has been broadly adapted to describe any tumour-related constituents circulating in body fluids such as CTC, DNA, RNA and exomes [4]. Compared with tissue biopsies, liquid biopsies may

**Figure 1.** *Emerging ctDNA applications in various CRC management settings.*

be better suited for serial surveillance, by reducing procedural time and potential harm. Blood sampling may also provide a more accurate representation of global tumoural heterogeneity, not limited to the site-specific characteristics detected through tissue biopsy [5]. The focus of this review will be directed towards circulating tumour DNA (ctDNA) found in blood samples, which at present, of all the liquid biopsy approaches, has had the greatest clinical impact. CtDNA is thought to be released by tumour cells, containing tumour-specific genetic and epigenetic alterations [6]; and has been found to correlate with tumour stage, burden of disease and response to therapy in CRC [7].

Herein, we provide an overview of ctDNA technologies in use and highlight the emerging clinical applications of ctDNA in various CRC management settings (**Figure 1**). The future directions of this rapidly advancing field will also be explored.
