ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Clonal evolution from primary to locally recurrent rectal cancer reveals recurrence-acquired potentially actionable alterations in treatment-naïve tumors.Journal of gastroenterology · 2026Article
- A vitronectin-functionalized ECM-mimetic hydrogel platform for modelling integrin-dependent tumour responses to cilengitide.Materials today. Bio · 2026Article
- Lorlatinib monotherapy or combination therapy in anaplastic lymphoma kinase-driven high-risk neuroblastoma.NPJ precision oncology · 2026Article
- From concept to clinic: emerging paradigms and novel insights into liquid biopsy.Cancer biology & medicine · 2026Article
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- Copy-Number Aberrations in Circulating Tumor DNA Enable Diagnosis and Risk Stratification of Pediatric Neuroblastic Tumors.Cancer research communications · 2026Article
- The Clinical Utility of Cell-Free DNA in Brain Tumor Management: A Comprehensive Review.Journal of molecular neuroscience : MN · 2025Review
- Detection of Targetable Genetic Abnormalities in Neuroblastoma Circulating Tumour DNA.International journal of molecular sciences · 2025Article
- Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth.Cell death & disease · 2025Article
- Stratified Medicine Pediatrics: Cell-Free DNA and Serial Tumor Sequencing Identifies Subtype-Specific Cancer Evolution and Epigenetic States.Cancer discovery · 2025Article
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- Demonstrating the Absence of Correlation Between Molecular Docking and in vitro Cytotoxicity in Anti-Breast Cancer Research: Root Causes and Practical Resolutions.Breast cancer (Dove Medical Press) · 2025Review
- [The role of clonal hematopoiesis in the molecular diagnostics of solid tumors].Magyar onkologia · 2024Review
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34 authors.
Funding
Abstract
purposeThe study of cell-free DNA (cfDNA) enables sequential analysis of tumor cell-specific genetic alterations in patients with neuroblastoma. EXPERIMENTAL
designEighteen patients with relapsing neuroblastoma having received lorlatinib, a third-generation ALK inhibitor, were identified (SACHA national registry and/or in the institution). cfDNA was analyzed at relapse for nine patients and sequentially for five patients (blood/bone marrow plasma) by performing whole-genome sequencing library construction followed by ALK-targeted ddPCR of the hotspot mutations [F1174L, R1275Q, and I1170N; variant allele fraction (VAF) detection limit 0.1%] and whole-exome sequencing (WES) to evaluate disease burden and clonal evolution, following comparison with tumor/germline WES.
resultsOverall response rate to lorlatinib was 33% (CI, 13%-59%), with response observed in 6/10 cases without versus 0/8 cases with MYCN amplification (MNA). ALK VAFs correlated with the overall clinical disease status, with a VAF < 0.1% in clinical remission, versus higher VAFs (>30%) at progression. Importantly, sequential ALK ddPCR detected relapse earlier than clinical imaging. cfDNA WES revealed new SNVs, not seen in the primary tumor, in all instances of disease progression after lorlatinib treatment, indicating clonal evolution, including alterations in genes linked to tumor aggressivity (TP53) or novel targets (EGFR). Gene pathway analysis revealed an enrichment for genes targeting cell differentiation in emerging clones, and cell adhesion in persistent clones. Evidence of clonal hematopoiesis could be observed in follow-up samples.
conclusionsWe demonstrate the clinical utility of combining ALK cfDNA ddPCR for disease monitoring and cfDNA WES for the study of clonal evolution and resistance mechanisms in patients with neuroblastoma receiving ALK-targeted therapy.
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