The Potential of Cell-Free DNA in Cancer: towards Standardization and Optimization for Enhanced Diagnosis and Monitoring

Abstract

Background: Cancer, characterized by the rapid and abnormal growth of cells affecting any part of the body, stands as the leading cause of death worldwide. Cell-free DNA (cfDNA) has garnered significant attention as a non-invasive liquid biopsy approach for disease detection, therapy evaluation, and prognosis. This review aims to provide a comprehensive exploration of cfDNA within the realm of oncology. It encompasses its diagnostic and therapeutic applications while identifying areas necessitating standardization and optimization. Methods: We reviewed existing literature to delve into the biological properties of cfDNA, exploring genetic and epigenetic aberrations found in various bodily fluids. Additionally, we explored its correlation with circulating tumor DNA (ctDNA). The review also encompasses preanalytical procedures and emerging technologies geared towards maximizing the complete potential of cfDNA. Results: Genetic and epigenetic markers have been identified in cfDNA across plasma, serum, and urine, presenting promising diagnostic and prognostic applications. Furthermore, ctDNA preserves genomic profiles akin to those found in corresponding tumor tissues, enabling a nuanced evaluation of tumor heterogeneity and mutation burdens. However, despite its potential, current methodologies suffer from a lack of standardization and optimization, thereby restraining the complete clinical utility of cfDNA. Conclusions: Although cfDNA stands as a compelling avenue for non-invasive early cancer diagnosis and therapy evaluation, unlocking its maximum potential requires methodological refinement and a deeper understanding of its biological characteristics. This review advocates for targeted research to standardize and optimize cfDNA analytical techniques, thereby enhancing its role in oncology.