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The DOI matches its Crossref record; 518 of the 519 references it cites were found in a registry or an index.

A comprehensive overview of liquid biopsy applications in pediatric solid tumors

Open access
Janssen, Ferdinand W., Lak, Nathalie S. M., Janda, Claudia Y., Kester, Lennart A., Meister, Michael T., Merks, Johannes H. M., van den Heuvel-Eibrink, Marry M., van Noesel, Max M., Zsiros, Jozsef, Tytgat, Godelieve A. M., Looijenga, Leendert H. J.·2024·npj Precision Oncology
DOI 10.1038/s41698-024-00657-zPMC PMC11297996
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Abstract

Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials.

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Crossref · 10.1038/s41698-024-00657-z

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Figures

Fig. 1 Graphical overview of liquid biopsy workflow for pediatric solid tumors. Frequent anatomical locations where pediatric solid tumors commonly present are indicated. Liquid biopsy matrices (e.g., peripheral blood, bone marrow, and CSF) are sampled and processed for isolation of analytes (e.g., ctDNA, CTCs, RNA (mRNA, miRNA, lncRNA), immune cells, and EVs) that are measured and characterized by specific methods (mostly PCR-based or sequencing-based) for biomarker analysis. The AI vector generator function from Adobe Illustrator was used for detailed visualization of this figure.
Fig. 1 Graphical overview of liquid biopsy workflow for pediatric solid tumors. Frequent anatomical locations where pediatric solid tumors commonly present are indicated. Liquid biopsy matrices (e.g., peripheral blood, bone marrow, and CSF) are sampled and processed for isolation of analytes (e.g., ctDNA, CTCs, RNA (mRNA, miRNA, lncRNA), immune cells, and EVs) that are measured and characterized by specific methods (mostly PCR-based or sequencing-based) for biomarker analysis. The AI vector generator function from Adobe Illustrator was used for detailed visualization of this figure.CC BY · PubMed Central
Fig. 2 Historical overview of publications focusing on liquid biopsies in pediatric solid tumors. In (a), the number of unique articles (y-axis) is plotted over time (x-axis), for studies and review articles. All articles used for this plot are also included in Table 1. All articles in the ‘studies’ plot are also included in (b) and Supplementary Tables 2–9. All articles in the ‘reviews’ plot are also included in Supplementary Table 10. In (b), The number of published studies (y-axis) is plotted over time (x-axis), for each tumor type. Studies that included pediatric patients for more than one tumor type are indicated in each respective plot. All studies used for this plot are also included in (a), Table 1, and Supplementary Tables 2–9.
Fig. 2 Historical overview of publications focusing on liquid biopsies in pediatric solid tumors. In (a), the number of unique articles (y-axis) is plotted over time (x-axis), for studies and review articles. All articles used for this plot are also included in Table 1. All articles in the ‘studies’ plot are also included in (b) and Supplementary Tables 2–9. All articles in the ‘reviews’ plot are also included in Supplementary Table 10. In (b), The number of published studies (y-axis) is plotted over time (x-axis), for each tumor type. Studies that included pediatric patients for more than one tumor type are indicated in each respective plot. All studies used for this plot are also included in (a), Table 1, and Supplementary Tables 2–9.CC BY · PubMed Central

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Citations

Cites

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Research works printed but not linked: 5

  1. WHO Classification of Tumours Editorial Board. Paediatric Tumours. Lyon (France): International Agency for Research on Cancer, 5th edn, Vol. 7 WHO classification of tumours series. https://publications.iarc.fr/608 (WHO, 2022).
  2. Mahapatra, S., Challagundla, K. B. Neuroblastoma. [Updated 2023 Jul 10]. In StatPearls [Internet]. Treasure Island (FL) (StatPearls Publishing 2024). Available from: https://www.ncbi.nlm.nih.gov/books/NBK448111/
  3. Kattuoa Ml, Dunton, C. J. Yolk Sac Tumors. In StatPearls [Internet]. Treasure Island (FL) (StatPearls Publishing, 2024). Available from: https://www.ncbi.nlm.nih.gov/books/NBK563163/
  4. Kaseb, H., Kuhn, J., Gasalberti, D. P. et al. Rhabdomyosarcoma. In StatPearls [Internet]. Treasure Island (FL) (StatPearls Publishing, 2024). Available from: https://www.ncbi.nlm.nih.gov/books/NBK507721/
  5. Carr, B. I. et al. HCC with low- and normal-serum alpha-fetoprotein levels. Clin. Pract. (Lond.) 15, 453–464 (2018).

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Metadata

Authors
Janssen, F. W., Lak, N. S. M., Janda, C. Y., Kester, L. A., Meister, M. T., Merks, J. H. M., van den Heuvel-Eibrink, M. M., van Noesel, M. M., Zsiros, J., Tytgat, G. A. M., & Looijenga, L. H. J.
Affiliations
  • Princess Máxima Center (NL)
  • Oncode Institute (NL)
  • Utrecht University (NL)
Corresponding author
Looijenga, Leendert H. J.
ORCID
Venue
npj Precision Oncology
Publisher
Springer Science and Business Media LLC
Published
2024-08-03
Volume
8
Issue
1
Pages
172-172
ISSN
2397-768X (ISSN-L)
DOI
10.1038/s41698-024-00657-z
PMC
PMC11297996
OpenAlex
W4401285140
Cited by
32
References
519
Citations by year
2026: 17 · 2025: 12 · 2024: 3
FWCI
1.56
Type
journal article
Language
en
Update notices
correction (2024-09-25)
Open access
Licence
Locations
  • npj Precision Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Stichting Kinderen Kankervrij
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
Keywords
liquid biopsy, pediatric solid tumors, tumor markers, neuroblastoma, kidney cancer, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, soft tissue sarcoma, liver tumors, circulating tumor DNA, cell-free DNA, microRNA, circulating tumor cells, clinical implementation, biomarker validation

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