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

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.