*Advances in the Molecular Understanding of Colorectal Cancer*

first-line treatment for metastatic colorectal cancer: Updated analysis of overall survival according to tumor KRAS and BRAF mutation status. Journal of Clinical Oncology. 2011;**29**(15):2011-2019

[79] Price TJ, Hardingham JE, Lee CK, Weickhardt A, Townsend AR, Wrin JW, et al. Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. Journal of Clinical Oncology. 2011;**29**(19):2675-2682

[80] Raponi M, Winkler H, Dracopoli NC. KRAS mutations predict response to EGFR inhibitors. Current Opinion in Pharmacology. 2008;**8**(4):413-418

**53**

Section 2

Biomarkers

Section 2 Biomarkers

*Advances in the Molecular Understanding of Colorectal Cancer*

first-line treatment for metastatic colorectal cancer: Updated analysis of overall survival according to tumor KRAS and BRAF mutation status. Journal of Clinical Oncology.

[79] Price TJ, Hardingham JE, Lee CK, Weickhardt A, Townsend AR, Wrin JW, et al. Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. Journal of Clinical Oncology.

[80] Raponi M, Winkler H, Dracopoli NC. KRAS mutations predict response to EGFR inhibitors. Current Opinion in Pharmacology. 2008;**8**(4):413-418

2011;**29**(15):2011-2019

2011;**29**(19):2675-2682

**52**

**55**

**Chapter 4**

**Abstract**

technologies may take.

**1. Introduction**

larly in the case of metastatic disease [3].

Current Utility and Future

*Daphne Day, Sophia Frentzas, Cameron A. Naidu,* 

Circulating tumour DNA (ctDNA) shows promise as a minimally invasive biomarker with a myriad of emerging applications including early detection and diagnosis, monitoring of disease and treatment efficacy, and identification of actionable alterations to guide treatment. The potential utility of ctDNA in colorectal carcinoma (CRC) is of particular interest given the limitations of current radiographic imaging and blood-based tumour markers in detecting disease and evaluating therapeutic benefit. While ctDNA has yet to demonstrate clinical utility in CRC, a growing body of research highlights the potential of these novel biomarkers. This chapter provides an overview of the current evidence for employing ctDNA in CRC as well as previewing the future directions that these exciting

**Keywords:** colorectal carcinoma/cancer, circulating tumour DNA, biomarker

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, particu-

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

Applications of ctDNA in

Colorectal Cancer

*Eva Segelov and Maja Green*
