| dc.description.abstract | In Neuroblastoma (NB), treatment burden reaches its limit, especially in high-risk (HR) patients with poor prognoses. Molecular characterization may help to identify new predictive biomarkers. Study MAPPYACTS showed that 15% of pediatric cancer patients at relapse proposed a targeted treatment matched to molecular profiling, however the overall gain in survival is limited. In the COMPASS project, the aim is to build an international, standardized and validated drug sensitivity platform based on image and molecular analysis with the ultimate goal of discovering new biomarkers and increase predictive power. This ex vivo high throughput drug screening and profiling is performed by using patient-derived xenografts (PDXs), with the ultimate goal to use fine needle aspiration (FNA) directly from patients and test whole drug libraries within a short timeframe.
In this context, the ultimate aim of this study is to establish a drug sensitivity and resistance microfluidics platform for drug sensitivity profiling in NB patients by using primary patients derived tumor cultures. The validation of workflow, protocols and optimization of best spheroid conditions for drug screening in microfluidic chips (Okomera) and 384 ULA well plates (Biophenics) is performed in NB PDX spheroid cultures. Different parameters are tested; optimal medium, extracellular matrices (ECM), number of cells, mouse cell depletion kits. Finally, a proof of concept with a single chemotherapy is performed to test workflow.
Results show that the use of serum-enriched medium (10% FBS) and low concentrations of Collagen I in culture, show better viability over time. Optimal number of cells is established at 40 cells/trap (Okomera) and varies for Biophenics. For the Biophenics part the mouse cell depletion kits help in spheroid formation and use lower amount of cells effectively. When optimizing the workflow and testing drug libraries on NB PDX spheroids, this procedure will be applied to study drug response directly on patients’ material and then help to discover new predictive biomarkers. This is an important step to personalized therapeutic care strategies in clinical settings for NB patients. | |
