Circulating tumor DNA and their added value in molecular oncology

Abstract

New methods for molecular diagnosis are now available in oncology thanks to the discovery of circulating tumor DNA molecules in the plasma of cancer patients. By utilizing blood samples, rather than traditional tissue sampling, clinical practice is on the verge of new discoveries from the analysis of cell-free DNA (cfDNA). The method, known as a “liquid biopsy”, consists of analyzing therapeutic targets and drug-resistant conferring gene mutations in circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA). These are subsequently released from primary tumors and metastatic deposits into the peripheral blood. The advantages of the method can be observed in the diagnosis, but also in the choice of treatment for solid tumors (e.g. non-small cell lung carcinomas [NSCLC]). In order to interpret the results, an understanding of the biological characteristics of circulating tumor DNA is required. Currently there is no consensus as to how a liquid biopsy should be conducted. In this review, we will assess the pros of ctDNA as analytes in peripheral blood samples and its impact on clinical applications in solid tumors and hematological malignancies. We will also address practical issues facing clinical implementation, such as pre-analytical factors. Moreover, we will emphasize the open questions that remain when considering the current state of personalized medicine and targeted therapy.

Comparative study on the mutation spectrum of tissue DNA and blood ctDNA in patients with non-small cell lung cancer

“…Existing studies indicate that gene mutations are tumor-specific and detection of mutations in local tumor tissues is often insufficient ( 17 , 18 ). Assessing these changes in ctDNA can provide greater diagnostic accuracy than standard protein biomarkers such as carcinoembryonic antigen (CEA) ( 19 , 20 ).…”

Osimertinib-Centered Therapy Against Uncommon Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer- A Mini Review

“…Liquid biopsy profiles the genetic features of circulating carcinoma cells, which has advanced the understanding of precision medicine. Compared with traditional tissue biopsy, liquid biopsy has an easier method for sampling and enables faster identification of mutations that confer sensitivity or resistance to osimertinib treatment ( 45 ).…”

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

“…Despite all the potential advantages of liquid biopsy in the management of CRC, there are still some practical issues that need to be addressed before it can be widely used in clinical practice [ 96 ]. Potential challenges may include low amounts of CTCs and ctDNA in samples, lack of pre-analytical and analytical consensus, clinical validation, regulatory endorsement and cost effectiveness [ 97 , 98 ]. Currently, the use of CTCs in routine diagnostics is limited, mainly due to methodological constraints, such as the lack of an established assessment practice, beyond enumeration [ 99 , 100 ].…”