Liquid biopsy and minimal residual disease — latest advances and implications for cure

ABSTRACT Liquid biopsy has been introduced as a new diagnostic concept predicated on the analysis of circulating tumour cells (CTCs) or circulating tumour-derived factors, in particular,

cell-free tumour DNA (ctDNA). Highly sensitive liquid biopsy assays have been developed that can now be applied to detect and characterize minimal residual disease (MRD), which reflects the

presence of tumour cells disseminated from the primary lesion to distant organs in patients who lack any clinical or radiological signs of metastasis or residual tumour cells left behind

after local therapy that eventually lead to local recurrence. This application is the new frontier of liquid biopsy analyses, which are challenged by the very low concentrations of CTCs and

ctDNA in blood samples. In this Review, we discuss the key technologies that can be used to detect and characterize CTCs in surveillance of MRD and provide a brief overview of similar roles

of ctDNA analyses. We then focus on the current clinical data on the use of CTCs and ctDNA in the detection and monitoring of MRD and in obtaining information on therapeutic targets and

resistance mechanisms relevant to the management of individual patients with cancer. KEY POINTS * Minimal residual disease (MRD) can be defined as cancer persisting in a patient after

treatment that cannot be detected with current medical imaging modalities and is, therefore, an occult stage of cancer progression. * Liquid biopsy approaches based on the detection of small

numbers of circulating tumour cells (CTCs) or minute amounts of circulating cell-free tumour DNA (ctDNA) now enable MRD detection in patients with various malignancies. * CTC detection at

primary diagnosis of cancer predicts an unfavourable prognosis and is, therefore, applicable to risk stratification strategies beyond the current approaches to tumour staging. * Monitoring

of CTCs and ctDNA during post-surgical follow-up assessments can enable the detection of disease relapse many months earlier than is possible with current radiological imaging procedures. *

Further characterization of CTCs and ctDNA can provide insights into the molecular evolution of MRD during tumour progression, with implications for therapy to delay or even prevent

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CONTENT BEING VIEWED BY OTHERS MINIMAL RESIDUAL DISEASE AS A TARGET FOR LIQUID BIOPSY IN PATIENTS WITH SOLID TUMOURS Article 28 November 2024 LIQUID BIOPSY ENTERS THE CLINIC — IMPLEMENTATION

ISSUES AND FUTURE CHALLENGES Article 20 January 2021 THE BREAST IS YET TO COME: CURRENT AND FUTURE UTILITY OF CIRCULATING TUMOUR DNA IN BREAST CANCER Article 26 May 2021 REFERENCES * Pan,

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(2017). PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS The authors thank N. Reimers for her assistance in designing figure 4. The authors received support from

the German Cancer Aid Fund (Deutsche Krebshilfe); DFG (Deutsche Forschungsgemeinschaft); the French National Institute of Cancer (INCa); CANCER-ID, an Innovative Medicines Initiative Joint

Undertaking under grant agreement no. 115749, resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007-2013) and European

Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contributions; and the European Liquid Biopsies Academy (ELBA) Innovative Training Networks (ITN) Horizon

2020 project H2020-MSCA-ITN-2017 (Towards widespread clinical application of blood-based diagnostic tools). COMPETING INTERESTS K.P. and C.A.-P. have ongoing patent applications related to

circulating tumour cells. K.P. has received honoraria from Agena, Novartis, Roche and Sanofi and research funding from European Federation of Pharmaceutical Industries and Associations

(EFPIA) partners (Angle, Menarini and Servier) of the CANCER-ID programme of the European Union–EFPIA Innovative Medicines Initiative. C.A.-P. has received honoraria from Janssen. REVIEWER

INFORMATION _Nature Reviews Clinical Oncology_ thanks J.-Y. Pierga and other anonymous reviewer(s) for their contribution to the peer review of this work. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany Klaus Pantel * Laboratory of Rare Human Circulating Cells (LCCRH), University

Medical Centre and University of Montpellier, Montpellier, France Catherine Alix-Panabières Authors * Klaus Pantel View author publications You can also search for this author inPubMed 

Google Scholar * Catherine Alix-Panabières View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Both authors made substantial contributions to

all stages of the preparation of this manuscript. CORRESPONDING AUTHOR Correspondence to Klaus Pantel. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to

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THIS ARTICLE Pantel, K., Alix-Panabières, C. Liquid biopsy and minimal residual disease — latest advances and implications for cure. _Nat Rev Clin Oncol_ 16, 409–424 (2019).

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