Advancing Liquid Biopsies for Monitoring and Personalized Treatment of Children with Neuroblastomas

Project Coordinator:
Hedi Deubzer (Germany), Charité – Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Pediatric Hematology/Oncology/SCT, Berlin

Project Partners:
Gudrun Schleiermacher (France), Institut Curie, Département d'Oncologie Pédiatrique et INSERM U830, Paris
Jaime Font de Mora (Spain), Hospital Universitario La Fe - HULAFE, Clinical and Translational Research on Cancer, Laboratory of Cellular and Molecular Biology, Valencia
Jo Vandesompele (Belgium), Ghent University, Department of Biomolecular Medicine, Gent
Sabine Taschner-Mandl (Austria), Children’s Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department for Tumor Biology, Vienna
Gam Tytgat (Netherlands), Prinses Máxima Centrum voor kinderoncologie, Department of Solid Tumors, Utrecht

Project Abstract:
The embryonal tumor, neuroblastoma, accounts for 11% of all cancer-related deaths in children. Its heterogeneous tumor biology creates clinical variability spanning spontaneous regression to rapid metastasizing progression. Long-term survival of high-risk disease remains poor, with <40% overall survival after first-line treatment and <10% after relapse, despite considerable international efforts to improve treatment over the last decades. Liquid biopsies have the power to revolutionize clinical care for children with high-risk neuroblastoma by reflecting precise disease status at any time during treatment and care. Blood and bone marrow samples are a less invasive source of biomarkers for patient monitoring and therapeutic decision-making. The LIQUIDHOPE consortium combines internationally recognized experts in neuroblastoma pan-omics and computational discovery with leading pediatric oncologists to advance this emerging clinical paradigm change. LIQUIDHOPE aims to accelerate transfer of liquid biopsy approaches into the clinic within 3 parallel research arms designed to overcome current hurdles in (1) therapy response assessment, (2) minimal residual disease (MRD) monitoring and (3) actionable target identification, and define the best marker/analysis method or combination thereof for patient monitoring as its secondary aim. LIQUIDHOPE will apply targeted metabolomics; cfDNA whole-exome sequencing; cfDNA transcriptional start site and methylation profiling; unbiased total RNA profiling to monitor long noncoding and circular RNA disease markers; droplet digital PCR of DNA/RNA disease markers; automated multiple marker imaging and sophisticated bioinformatics. LIQUIDHOPE can identify and validate predictive markers for treatment response, MRD, relapse and treatment choice in blood/bone marrow surrogates to advance unique liquid biopsy-based innovations for patient monitoring and personalized treatment of children battling neuroblastoma.


(Project funded under JTC 2017)