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.

Liquid biopsy based biomarkers in non-small cell lung cancer for diagnosis and treatment monitoring

“…Liquid biopsy analysis is a rapidly expanding field in translational cancer research and might be useful at different points of the diagnostic/ therapeutic course of cancer patients, such as early diagnosis, estimation of the risk for metastatic relapse or metastatic progression (prognostic information), stratification and real-time monitoring of therapies, identification of therapeutic targets and resistance mechanisms (predictive information), and understanding metastasis development in cancer patients. Different liquid-derived materials can be employed, such as CTCS, ctDNA, exosomes, circulating RNA or microRNAs (9). They may be obtained from almost all body fluids (blood, serum, plasma, urine, pleural effusion, ascites, etc.)…”

“…CTCs have long been considered to reflect tumor aggressiveness and have been investigated as a surrogate marker for tumor growth. At this respect, the decrease in the number of CTCs during the treatment has been associated with radiographic tumor response and an increase in the cell counts with tumor progression (9). In particular, the decrease or disappearance of CTCs following surgery has been correlated with improved clinical outcomes (28,29).…”

Quality control materials for pharmacogenomic testing in the clinic

“…Cell-free tumor DNA is a promising liquid biopsy with numerous advantages over invasive biopsies [50]. As a non-invasive biomarker, ctDNA provides information about mutations that are highly consistent with those of the paired tumors, which can be used to monitor tumor dynamics and track the development of acquired resistance.…”

Clinical and Investigational Applications of Liquid Biopsy in Non-Small Cell Lung Cancer

“…CTCs have long been considered to reflect tumor aggressiveness. In this regard, the decrease in the number of CTCs during different treatments (surgery, chemotherapy, radiotherapy, etc) has been associated with radiographic tumor response while increase in the number of cells has been correlated with tumor progression [12] . CTCs detection and characterization represent a major challenge as they may comprise both the phenotypic and genetic information of the primary tumors.…”

“…Nevertheless, ctDNA-based assays are confronted with several challenges. Body cells release cfDNA into the bloodstream, but the majority of cfDNA is often not of cancerous origin, making it sometimes difficult to detect [12] . Also, prior knowledge about particular mutations is usually required, which may be hard to obtain.…”