Circulating tumor DNA as an early marker of therapeutic in patients with metastatic colorectal cancer

Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer-related mortality in the world. Approximately half of CRC patients develop metastatic disease. Since the metastasis may be lethal, causing mass-impact and interfering with homeostasis, its development is a concern for clinicians and patients. Over the past decade, advances in systemic therapeutic options have improved outcomes of patients with metastatic CRC (mCRC). One important goal of treatment strategy of mCRC patients is to enhance survival while maintaining the life quality and avoiding unnecessary toxic impacts of an ineffective treatment. To achieve this point, the early assessment of therapeutic efficacy is a central aspect in the management strategy of patients. The gold standard for response assessment and treatment efficacy of CRC patients is the radiographic imaging. However, there are some limitations to its use. Recently, several attempts have been made to establish minimal or noninvasive biomarkers for evaluation of response to therapy. Circulating tumor DNA (CtDNA), tumor-derived fragmented DNA, generally represents a small fraction (<1%) of the total circulating DNA. Recent studies have been shown that CRC patients had higher total concentration of circulating DNA compared with healthy people. Furthermore, patients with advanced or metastatic CRC had higher circulating DNA concentration compared with patients with localized CRC. It has additionally been demonstrated that a part of this circulating DNA is carrying specific tumor genetic alterations. The amount of tumor-derived DNA in the bloodstream was hence proposed as being a surrogate marker of monitoring tumor burden or response during treatment and tracking resistance and tailoring treatment.