Advancing liquid biopsies for monitoring and personalized treatment of children with neuroblastomas
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.
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This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 964264.