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Circulating cell-free DNA (cfDNA) comprises extracellular DNA fragments released into bodily fluids through cellular processes such as apoptosis, necrosis, and active secretion. Alterations in cfDNA concentration, fragmentation patterns, and molecular characteristics under physiological and pathological conditions, including pregnancy-related disorders, have established its value as a minimally invasive biomarker for early disease detection and clinical monitoring. Due to the availability of non- or minimally-invasive and scalable detection platforms with high sensitivity and specificity, cfDNA has emerged as a powerful tool in maternal-fetal medicine. This review provides a comprehensive overview of recent advances in cfDNA research, with an emphasis on its applications in pregnancy-related disorders. We elucidate the underlying biological mechanisms, current diagnostic and prognostic uses, analytical technologies, and the key challenges and future directions for clinical translation.
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http://dx.doi.org/10.3389/fcell.2025.1600532 | DOI Listing |
Cancer Discov
September 2025
IFOM-ETS The AIRC Institute of Molecular Oncology, Milan, Italy.
Wang and colleagues showed that ctDNA can be detected in plasma up to 3 years prior to clinical diagnosis. The study highlights the need for ultrasensitive and multimodal approaches that integrate the detection of mutations and copy-number changes with advanced computational platforms to deliver effective early-detection strategies. See related article by Wang et al.
View Article and Find Full Text PDFMed Oncol
September 2025
Chemistry Department, Faculty of Science, Cairo University, Cairo, Egypt.
Pancreatic cancer is among the most lethal forms of cancer, with a five-year survival rate under 7%, primarily due to its late clinical presentation and rapid disease progression. Although the oncogenic development of pancreatic tumors can span over a decade, early diagnosis remains a major clinical challenge, as current diagnostic approaches-including imaging modalities and blood-based markers like CA19-9-lack the requisite sensitivity for detecting early-stage disease. Liquid biopsy has emerged as a promising, non-invasive diagnostic technique by enabling the detection of circulating tumor-specific nucleic acids, particularly circulating tumor DNA (ctDNA) and microRNAs (miRNAs).
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, United States.
Purpose/objectives: Cancer screening continues to be a major challenge, with reliable tests only being available for very few cancers. Multi-cancer early detection (MCED) genomic tests are being developed that allow for blood-based screening of multiple cancers simultaneously. The PATHFINDER study was a multi-institution prospective cohort study in healthy participants over the age of 50 years (no cancer history, or history of treated cancer > 3 years prior), investigating the feasibility of the Galleri (GRAIL, LLC) cfDNA methylation MCED blood test.
View Article and Find Full Text PDFFront Transplant
August 2025
Department of Cardiovascular Disease, Inova Schar Heart and Vascular, Falls Church, VA, United States.
Despite significant advances in organ preservation, surgical techniques, and immunosuppressive regimens, rejection continues to pose a major challenge in the care of heart transplant patients. Endomyocardial biopsy (EMB) remains the gold standard test for surveillance and diagnosis of rejection, but is limited by its invasiveness, interobserver variability, procedural risk, and cost thus prompting the widespread use of non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA). Due to its high negative predictive value, dd-cfDNA is often routinely used for surveillance of asymptomatic patients.
View Article and Find Full Text PDFPathogens
August 2025
Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92093, USA.
Background: The Karius Test (KT), a microbial cell-free DNA next-generation sequencing assay, is increasingly utilized in challenging infectious syndromes. However, its real-world clinical utility and cost-effectiveness remain uncertain.
Methods: We conducted a retrospective review of 88 KT results from adult patients at UC San Diego Health between July 2017 and April 2024.