Life sciences · Journal article
International Journal of Molecular Sciences · September 14, 2026
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The detection of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) is a minimally invasive approach for diagnosing and monitoring cancer. These liquid biopsy-based strategies enable the identification of primary or metastatic tumors and provide valuable information on tumor biology and treatment response. A variety of techniques are employed to analyze components obtained through liquid biopsy. While CTCs are typically detected using cell-based methods, ctDNA is commonly analyzed using highly sensitive molecular approaches, including quantitative PCR (qPCR), digital PCR (dPCR), and next-generation sequencing (NGS). Extracellular vesicles (EVs), which carry tumor-derived nucleic acids, proteins, and other biomolecules, are increasingly investigated as potential biomarkers, while tumor-educated platelets (TEPs) can reflect tumor-associated molecular changes and may provide additional information for cancer detection and monitoring. Furthermore, emerging multi-cancer early detection (MCED) approaches aim to identify molecular signatures associated with multiple cancer types from a single blood sample, highlighting the broader diagnostic potential of liquid biopsy. Due to the high specificity of tumors and somatic mutations, ctDNA serves as a real-time biomarker for tracking cancer progression. The advantages of ctDNA diagnostics include its low invasiveness and its capacity to detect cancer at early stages. In addition to confirming the presence of a tumor, liquid biopsy approaches facilitate the assessment of malignancy and the evaluation of treatment response. In the field of human medicine, ctDNA plays a pivotal role in diagnostic procedures. It is utilized not only for screening tests that detect the presence of cancer but also for the development of targeted treatment protocols for specific patients. These protocols are informed by the detection of genomic alterations and are designed to monitor the response to therapy over the course of treatment. Similarly, CTC, EV, TEP, and MCED approaches are being investigated as complementary tools for cancer detection, molecular characterization, prognosis, and longitudinal disease monitoring. In the domain of veterinary medicine, ctDNA has been instrumental in the diagnosis of various neoplasms, including osteosarcomas, hemangiosarcomas, lymphomas, canine mammary tumors, and melanomas. Other liquid biopsy components, including CTCs and EVs, also show promise for the detection and characterization of tumors in companion animals, although their clinical application remains less developed than in human medicine. Another significant application is in the detection of minimal residual disease (MRD), where a small number of cancer cells remain undetectable by conventional tests, such as blood counts. This underscores the significance of advanced ctDNA analysis. However, challenges persist, including the low concentration of ctDNA in blood, the low ratio of mutated to normal DNA fragments, potential contamination, biological variability, and the need for standardized protocols. This review synthesizes the current knowledge on liquid biopsy, including ctDNA, CTCs, EVs, TEPs, and emerging MCED approaches, and the potential for transferring these technologies from human medicine to animal medicine. Continued research is necessary to enhance the sensitivity and specificity of detection, which could facilitate early cancer diagnosis in animals and improve survival through timely treatment.