Cell-free circulating tumor DNA in cancer

Abstract

Cancer is a common cause of death worldwide. Despite significant advances in cancer treatments, the morbidity and mortality are still enormous. Tumor heterogeneity, especially intratumoral heterogeneity, is a significant reason underlying difficulties in tumor treatment and failure of a number of current therapeutic modalities, even of molecularly targeted therapies. The development of a virtually noninvasive “liquid biopsy” from the blood has been attempted to characterize tumor heterogeneity. This review focuses on cell-free circulating tumor DNA (ctDNA) in the bloodstream as a versatile biomarker. ctDNA analysis is an evolving field with many new methods being developed and optimized to be able to successfully extract and analyze ctDNA, which has vast clinical applications. ctDNA has the potential to accurately genotype the tumor and identify personalized genetic and epigenetic alterations of the entire tumor. In addition, ctDNA has the potential to accurately monitor tumor burden and treatment response, while also being able to monitor minimal residual disease, reducing the need for harmful adjuvant chemotherapy and allowing more rapid detection of relapse. There are still many challenges that need to be overcome prior to this biomarker getting wide adoption in the clinical world, including optimization, standardization, and large multicenter trials.

Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients

“…Highly sensitive detection methods like digital PCR are needed in order to detect rare MT targets within high concentrations of WT background [31]. WT background size (i.e.…”

Circulating Free DNA in Serum and Genomic Alterations of Lung Cancer Patients and High Risk Individuals Exposed to Environmental Pollution

“…The small DNA fragments, called cfDNA, are released into the circulation as a consequence of necrosis, apoptosis and/or active secretion from cells in a tumorigenesis or inflammation process [70][71][72]. These genomic fragments could be present in cancer free patients, but in cancer patients a significant fraction shall come from tumor cells [72].…”

Potential of Liquid Biopsies for Breast Cancer Screening, Diagnosis, and Response to Treatment

“…These alterations can be detected in the form of point mutations, copy number variations, chromosomal rearrangements, or altered methylation patterns. Moreover, ctDNA has a relatively short half-life, ranging from 15 min to approximately 2 h, and can therefore be used as a dynamic biomarker for accurate monitoring of tumor masses in real time [reviewed in 9]. One major challenge is the detection of ctDNA, as it is composed of small fragments of 180 bp on average and can represent as little as 0.01% of the total circulating DNA, termed cfDNA [13].…”

“…ctDNA in the blood of patients with cancer is derived from tumor necrosis, tumor cell apoptosis, and/or direct secretion of DNA by tumor cells [9]. Methylation, mutations, microsatellite alterations, DNA integrity, and viral DNA can be studied in ctDNA – the contributing factors of tumor DNA released into the circulation, which are tumor burden and tumor cell proliferation [8].…”