Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer

Abstract

Tissue biopsy is the standard diagnostic procedure for cancers and also provides a material for genotyping, which can assist in the targeted therapies of cancers. However, tissue biopsy-based cancer diagnostic procedures have limitations in their assessment of cancer development, prognosis and genotyping, due to tumor heterogeneity and evolution. Circulating tumor DNA (ctDNA) is single- or double-stranded DNA released by the tumor cells into the blood and it thus harbors the mutations of the original tumor. In recent years, liquid biopsy based on ctDNA analysis has shed a new light on the molecular diagnosis and monitoring of cancer. Studies found that the screening of genetic mutations using ctDNA is highly sensitive and specific, suggesting that ctDNA analysis may significantly improve current systems of tumor diagnosis, even facilitating early-stage detection. Moreover, ctDNA analysis is capable of accurately determining the tumor progression, prognosis and assisting in targeted therapy. Therefore, using ctDNA as a liquid biopsy may herald a revolution for tumor management. Herein, we review the biology of ctDNA, its detection methods and potential applications in tumor diagnosis, treatment and prognosis.

Keywords: biology; biomarker; circulating tumor DNA; liquid biopsy; targeted therapies.

Figure 1. The potential origins of ctDNA and the hypothesis of genometastasis

Three potential origins of ctDNA: (1) apoptotic tumor cells, (2) Living tumor cells, and (3) circulating tumor cells. Additionally, according to the hypothesis of genometastasis, ctDNA may transform normal cells to tumor cells, resulting in distant metastasis.