A Review of the Role of Circulating Tumor DNA (ctDNA) Biomarkers in Cancer

Early diagnosis is one of the most important factors in cancer patients’ treatment. Early detection of cancer requires the discovery of sensitive and specific biomarkers. These biomarkers include proteins (i.e., enzymes, receptors, antibodies and peptides), nucleic acids (DNA- based, such as cell-free DNA (cfDNA) or could be RNA-based, such as microRNA or other non-coding RNAs).  In this review, we investigated the role of circulating tumor DNA (ctDNA) biomarker in the diagnosis of cancer.

In order to find articles related to the purpose of the research, keywords ctDNA and cancer and diagnosis were searched in Google Scholar, PubMed and Web of Science databases. After reviewing 312 found articles, the articles without exact subject and purpose relevance were excluded from the study. Finally, 174 related articles were included in the study. After linking the findings, the articles were read and the desired content was adapted.

It seems that cfDNA is the result of DNA fragmentation after apoptosis, necrosis, active secretion and damage or death of cells and different tissues and is released into the bloodstream. cfDNA is also used as a biomarker for the diagnosis, recurrence and prognosis of some cancers. Also, ctDNA is a part of cfDNA, which includes small pieces of DNA with a length of less than 200 nucleotides. ctDNA is derived from tumor cells circulating in the bloodstream and lymphatic system. Also, ctDNA may be released directly from cells in the tumor site that are dying due to apoptosis and necrosis, or through active release from healthy tumor cells in the bloodstream and lymphatic system. The amount of ctDNA in different people is different and depends on the type of tumor, its location and for cancerous tumors, the stage of the cancer. Assessing the amount of ctDNA, tracking its mutations and investigating the occurrence of aberrant methylation of ctDNA are important biomarkers in diagnosis, determining prognosis, and the course of treatment for cancer patients. Controlling cancers by measuring dynamic ctDNA in blood, plasma or serum is a new and developing area of research.

It seems that despite the challenges in the clinical application of ctDNAs, they can be used in the early diagnosis of cancer.