Circulating Tumor DNA detection in cancer - a comprehensive overview of current detection methods and prospects

Sep 23, 2026

Uploaded by Franzy

The analysis of circulating tumor DNA (ctDNA) has emerged as a major minimally invasive biomarker in oncology. Numerous detection strategies can be selected based on the specific oncological context. PCR-based approaches are favored for sensitivity and cost-effectiveness but cover a narrower gene range, while NGS-based methods support comprehensive cancer genotyping and identification of actionable mutations. Emerging techniques such as third-generation sequencing and fragmentomics increase technical complexity. Overall, the review evaluates advantages and limitations across detection strategies to improve clinical care.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Implications for practice

Introduction

Circulating Tumor DNA detection in cancer: a comprehensive overview of current detection methods and prospects Ana Regina de Abreu1,2,, AylaWyninckx1,2, Timon Vandamme2, Ken Op de Beeck1,2,, Guy Van Camp1,, Marc Peeters2, Pierre Laurent-Puig3, Julien Taieb3,, Valerie Taly3, Leonor Benhaim3,4, *, 1Center of Medical Genetics, Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem 2650, Belgium 2Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp and Antwerp University Hospital, Antwerp 2650, Belgium 3Équipe labélisée Ligue Nationale contre le cancer, Centre de Recherche des Cordeliers, UMR-S1138, CNRS SNC5096, Université de Paris, Paris 75005, France 4Department of Visceral and Surgical Oncology, Gustave Roussy, Cancer Campus, Villejuif 94805, France *Corresponding author: Leonor Benhaim, Équipe labélisée Ligue Nationale contre le cancer, Centre de Recherche des Cordeliers, UMR-S1138, CNRS SNC5096, Université de Paris, Paris 75005, France ([leonor.benhaim@gustaveroussy.fr](leonor.benhaim@gustaveroussy.fr)) . Abstract Complete oveview of ctDNA detection methods.The analysis of circulating tumor DNA (ctDNA) has emerged as a major minimally invasive biomarker in oncology. Numerous methods exist for ctDNA detection and should be selected based on the specific oncological context. PCR-based methods are often preferred for their sensitivity and cost-effectiveness; however, they are limited to a narrower range of genes. In contrast, NGS-based methods enable comprehensive cancer genotyping and more efficient identification of actionable mutations. Moreover, the growing number of emerging approaches, such as third-generation sequencing and fragmentomics, highlights the increasing technical complexity of ctDNA detection. Overall, this review provides insights into the advantages and limitations of various detection strategies that can help improve clinical care for patients. Key words: liquid biopsy; ctDNA; cancer; detection; clinical application. Implications for practice This manuscript describes the importance of accurate circulating tumor DNA (ctDNA) detection in our clinical practice, offering an in-depth review of both established and emerging ctDNA detection technologies. It explores their application across the continuum of cancer management, with particular attention to technical and practical considerations. As ctDNA plays an increasingly pivotal role in cancer diagnostics, this work provides crucial insights on the strengths and limitations of these methods to support clinical decision-making. Introduction Cancer remains one of the leading causes of mortality worldwide.1 Despite significant advancements in treatment, challenges persist. Early-stage cancers are often asymptomatic, and nearly half of all patients are diagnosed with metastatic stage, which underscores the limitations of current detection methods. Imaging techniques lack the required sensitivity for effective screening and minimal residual disease (MRD) detection. Hence, ongoing research focused on developing more sensitive and accessible biomarkers is essential. Cancer evolves through the accumulation of genetic and epigenetic alterations, which can be used for tumor detection and characterization. Single nucleotide variants (SNVs), methylation alterations, copy number alterations (CNAs), and gene fusions can be detected in tumor DNA, typically obtained through a tissue biopsy. However, relying on a tumor biopsy has its limitations, as it may not fully capture intra-or inter-tumoral heterogeneity. The concept of “liquid biopsy,” introduced in 2019, was originally associated with the analysis of circulating tumor cells (CTCs) within blood samples. It was later extended to include the analysis of various circulating components, such as circulating tumor DNA (ctDNA), within various biological fluids.2–4 Although blood remains

FAQs

What makes circulating tumor DNA (ctDNA) important in oncology?

ctDNA provides a minimally invasive biomarker and can support screening, diagnosis, and treatment monitoring. Its concentration relates to tumor localization and overall tumor burden.

How do PCR-based ctDNA detection methods compare with NGS-based methods?

PCR-based methods are often preferred for sensitivity and cost-effectiveness, but they are limited to a narrower range of genes. NGS enables comprehensive cancer genotyping and more efficient detection of actionable mutations.

Why is ctDNA detection more informative than traditional tissue biopsy?

Tissue biopsy assesses only a small fraction of the tumor, while ctDNA theoretically reflects the entire tumor genome and represents (sub)clones across tumor heterogeneity.

Sep 23, 2026

Uploaded by Franzy