The Role of Cell-Free DNA in Cancer Treatment Decision Making

Abstract

The aim of this review is to evaluate the present status of the use of cell-free DNA and its fraction of circulating tumor DNA (ctDNA) because this year July 2022, an ESMO guideline was published regarding the application of ctDNA in patient care. This review is for clinical oncologists to explain the concept, the terms used, the pros and cons of ctDNA; thus, the technical aspects of the different platforms are not reviewed in detail, but we try to help in navigating the current knowledge in liquid biopsy. Since the validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, ctDNA may be used for this soon in routine clinical practice and in other different areas as well. The cfDNA fragments can be obtained by liquid biopsy and can be used for diagnosis, prognosis, and selecting among treatment options in cancer patients. A great proportion of cfDNA comes from normal cells of the body or from food uptake. Only a small part (<1%) of it is related to tumors, originating from primary tumors, metastatic sites, or circulating tumor cells (CTCs). Soon the data obtained from ctDNA may routinely be used for finding minimal residual disease, detecting relapse, and determining the sites of metastases. It might also be used for deciding appropriate therapy, and/or emerging resistance to the therapy and the data analysis of ctDNA may be combined with imaging or other markers. However, to achieve this goal, further clinical validations are inevitable. As a result, clinicians should be aware of the limitations of the assays. Of course, several open questions are still under research and because of it cfDNA and ctDNA testing are not part of routine care yet.

Exploring the Role of Circulating Cell-Free DNA in Disease Diagnosis and Therapy

“…The rise of ccfDNA has been buoyed by advancements in genomic technologies, enabling the detection and analysis of these DNA fragments with unprecedented precision and sensitivity. Its emergence as a diagnostic tool is particularly transformative in oncology, where early detection and continuous monitoring of cancer are critical for successful treatment outcomes [4]. Unlike conventional methods, which often require invasive tissue biopsies and can be limited by tumor accessibility and heterogeneity, ccfDNA provides a holistic view of the tumor genome.…”

Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

“…cfDNA fragments bear unique genetic and epigenetic patterns characteristic to the tumor they originate [222,223]. Understanding of their physical properties and circulation dynamics can facilitate cfDNA optimization and refinement to harness effective theranostic uses [224,225]. Furthermore, kinetic evaluation and molecular profiling through BEAMing (beads, emulsions, amplification, and magnetics), next-generation sequencing (NGS), and digital droplet PCR (ddPCR) are potential non-invasive cancer management modalities.…”

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios

“…The applicability of cfDNA in the prediction of prognosis is another avenue that has been extensively studied in solid tumors with excellent correlation to tissue samples. Many studies have reported that baseline cfDNA concentrations prove to be valuable in the prediction of prognosis in solid tumors, especially renal, breast, genitourinary, and brain tumors ( De Mattos et al, 2011 ; Telekes and Horváth, 2022 ). The recent World Health Organization (WHO) classification update underscores the presence of recurrent mutations in several hematological malignancies ( Alaggio et al, 2022 ).…”