Evidence of cancer: a systematic review of metabolomics in extracellular vesicles for cancer biomarker detection

Mayhew, Megan; Megram, Oliver; Roshan, Simmie; Smith, Marshall J.; White, Sam; Wilson, Philippe B.; Hunt, John A.; De Girolamo, Luigi; James, Victoria; Hunter, Elena

Evidence of cancer: a systematic review of metabolomics in extracellular vesicles for cancer biomarker detection

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Official URL: https://doi.org/10.1007/s11306-025-02386-1

Abstract

Background: The early detection of cancer remains a critical challenge in clinical oncology, with significant implications for patient survival rates and treatment outcomes. Research focus has shifted to developing minimally invasive diagnostic approaches for cancer detection and prognosis, such as metabolomic analysis of biological fluids and tumour-derived components, including extracellular vesicles (EVs). EVs carry molecular cargo, including metabolites, that reflect the pathophysiological state of their cell of origin. Analysis and characterisation of these metabolites may offer novel insights into cancer biology and facilitate the identification of potential biomarkers. Aim of review: This review systematically examines existing literature on the metabolomic analysis of EVs in the context of cancer to obtain a deeper understanding of potential metabolite biomarkers associated with cancer. Key scientific concepts of review: A comprehensive search of PubMed, Scopus, and Web of Science was conducted using a defined strategy to identify studies analysing EV-derived metabolites in cancer. Twelve eligible studies were included, collectively reporting 1,602 identified metabolites across various cancer types, sample sources, EV isolation methods, and metabolomic techniques. Of these, 333 metabolites were reported to be differentially regulated in EVs derived from patients with cancer, or conditioned medium from cancerous cell lines and their respective healthy controls. The review highlights the potential of EV metabolomics to detect cancer biomarkers but also underscores methodological variability as a major limitation. Differences in isolation and analytical techniques likely contribute to inconsistent findings, emphasising the need for standardised protocols in future research.