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Minimal residual disease as a target for liquid biopsy in patients with solid tumours

Nature Reviews Clinical Oncology volume 22, pages 65–77 (2025)Cite this article

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Abstract

Metastasis is the leading cause of cancer-related death in patients with solid tumours. Current imaging technologies are not sufficiently sensitive to detect minimal residual disease (MRD; also known as measurable or molecular residual disease) after initial surgery or chemotherapy, pointing to the need for more sensitive tests to detect remaining traces of cancer in the body. Liquid biopsy, or the analysis of tumour-derived or tumour-induced cells or cellular products in the blood or other body fluids, has opened a new diagnostic avenue to detect and monitor MRD. Liquid biopsy is already used in clinical decision making for patients with haematological malignancies. Here, we review current knowledge on the use of circulating tumour DNA (ctDNA) to detect and monitor MRD in patients with solid tumours. We also discuss how ctDNA-guided MRD detection and characterization could herald a new era of novel ‘post-adjuvant therapies’ with the potential to eliminate MRD and cure patients before terminal metastatic disease is evident on imaging.

Key points

  • Sensitive blood assays enable the detection of circulating tumour DNA (ctDNA) at very low concentrations (down to <10 ppm).

  • The detection of very low concentrations of ctDNA is required to detect minimal residual disease (MRD; also known as measurable or molecular residual disease) in patients with solid tumours.

  • MRD detection can be correlated with clinical outcomes such as progression-free survival and overall survival.

  • ctDNA-based MRD detection can precede imaging-based detection of relapse by several months depending on the tumour type and stage.

  • The transition of ctDNA-detectable MRD to overt metastasis can depend on the residual tumour burden and the host response (for example, antitumour immunity).

  • Interventional clinical studies in patients with solid tumours and MRD positivity are now required to assess which treatment(s) can eliminate MRD in these patients.

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Fig. 1: The biology of MRD in patients with resected solid tumours.
Fig. 2: Evolution of MRD in patients with solid tumours.

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Acknowledgements

K.P. received funding from the Deutsche Forschungsgemeinschaft Priority Program SPP 2084 microBONE (DFG), Deutsche Krebshilfe project CUPIDO and the European Research Council (ERC) Advanced Investigator Grant INJURMET (no. 834974). C.A.-P. received funding from La Fondation ARC pour la Recherche sur le Cancer with the project “PANLIPSY” on liquid biopsy and pancreatic cancer, the Institut National du Cancer and from les Fonds de Dotation AFER pour la Recherche Médicale.

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Authors and Affiliations

  1. Department of Tumour Biology, University Medical, Center Hamburg-Eppendorf, Hamburg, Germany

    Klaus Pantel

  2. European Liquid Biopsy Society (ELBS), Hamburg, Germany

    Klaus Pantel & Catherine Alix-Panabières

  3. Laboratory of Rare Human Circulating Cells (LCCRH) and Liquid Biopsy, University Medical Centre of Montpellier, Montpellier, France

    Catherine Alix-Panabières

  4. CREEC (CREES), Unité Mixte de Recherches, IRD 224–CNRS 5290–Université de Montpellier, Montpellier, France

    Catherine Alix-Panabières

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Correspondence to Klaus Pantel or Catherine Alix-Panabières.

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Nature Reviews Clinical Oncology thanks A. A. Chaudhuri, Y. Nakamura, who co-reviewed with T. Hashimoto, C. Rolfo and A. Sartore-Bianchi for their contribution to the peer review of this work.

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Pantel, K., Alix-Panabières, C. Minimal residual disease as a target for liquid biopsy in patients with solid tumours. Nat Rev Clin Oncol 22, 65–77 (2025). https://doi.org/10.1038/s41571-024-00967-y

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