article · Journal of American Medical Science and Research.
Tissue biopsy remains the standard diagnostic approach in oncology but is invasive, spatially limited, and difficult to repeat for regular monitoring. While liquid biopsy offers a minimally invasive alternative, relying on a single analyte such as circulating tumour DNA can miss critical biological signals due to low shedding, noise, and tumour heterogeneity. Combining multiple markers, including circulating tumour DNA, circulating tumour cells, extracellular vesicles, microRNAs, and fragmentomics, provides a more comprehensive assessment. Evidence shows that multi-analyte testing outperforms single-analyte methods in screening, diagnosis, treatment selection, immunotherapy monitoring, and residual disease detection. Multi-marker panels and integrative models improve early detection sensitivity and outcome predictions. Realising the clinical value of these multi-analyte approaches requires standardised pre-analytical handling, harmonised analytical frameworks, artificial intelligence integration, and further trials tailored to diverse settings, including Sub-Saharan Africa.
Standard cancer biopsies are invasive and cannot easily track disease progression over time. Liquid biopsies that measure multiple biological signals simultaneously offer a less invasive and more reliable way to detect tumours early, select targeted treatments, and monitor responses. Developing these integrative testing strategies could help clinicians identify treatment failure earlier and tailor cancer care across diverse healthcare settings.
The abstract describes multi-analyte diagnostics ranging from existing panels like CancerSEEK to emerging multi-cancer early detection tests. These tools could be used by oncologists and clinical laboratories for early screening, therapy selection, and residual disease monitoring. However, real-world clinical adoption requires standardised pre-analytical methods, harmonised analytical platforms, artificial intelligence data integration, and future clinical trials, indicating that broad implementation remains an ongoing translation effort rather than an immediate off-the-shelf solution.
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Background: Tissue biopsy is the established diagnostic standard in oncology; however, it is invasive, limited in spatial and temporal scope, and frequently impractical for serial monitoring. Liquid biopsy provides a minimally invasive and repeatable method for assessing tumour biology. Dependence on a singular analyte, such as ctDNA, may overlook clinically significant signals attributable to tumour heterogeneity, low shedding, and biological noise. Objective: To synthesise evidence that supports the use of multi-analyte liquid biopsy, which integrates ctDNA, circulating tumour cells (CTCs), extracellular vesicles/exosomes, microRNAs (miRNAs), and fragmentomics/epigenomics for purposes including screening, diagnosis, treatment selection, response assessment, and minimal residual disease (MRD) detection. Methods: This narrative review examines peer-reviewed studies, guidelines, and key trials across various analytes and disease contexts, focusing on integrative methodologies and their relevance in diverse environments, particularly in Sub-Saharan Africa. Results: ctDNA has been verified for the selection of targeted therapies in advanced NSCLC and for MRD risk stratification in colorectal cancer; its integration with CTCs enhances MRD detection and prognostic evaluation. DNA methylation and fragmentomics, including DELFI, improve the ability to find things early. Exosomal PD-L1 and phenotyped circulating tumour cells (CTCs) contribute to refined resistance profiling and immunotherapy monitoring. Also, circulating miRNAs make early-signal sensitivity higher. Multi-analyte panels, such as Cancer SEEK/DETECT-A and methylation-based MCED paired with fragmentomics, work better than single-analyte testing in some cases. Integrative models, on the other hand, give more accurate forecasts of outcomes. Conclusion: Multi-analyte liquid biopsy is emerging as an essential element of precision oncology. Standardised pre-analytics, harmonised analytics, and AI-driven integration are essential for improving therapeutic utility across various populations. It is important to prioritise future trials and implementation that is appropriate for the situation, even in Sub-Saharan Africa.
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DOI: 10.51470/amsr.2025.04.02.67
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