MicroOrganoSphere™ technology to advance drug screening in neuroblastoma precision medicine

Background Neuroblastoma is among the most fatal pediatric solid tumors and high-risk patients face poor survival despite intensive treatment. Genomic profiling alone has not translated into effective treatment stratification for all neuroblastoma patients. Drug screening offers a complementary strategy, but conventional preclinical models are constrained by limited establishment success from low-input material and by timelines often incompatible with diagnostic decision-making. Here, we evaluated MicroOrganoSphere™ (MOS™) technology, in which tumor cells are encapsulated in Matrigel droplets generated by microfluidic droplet formation, by a head-to-head comparison with the conventional suspension cultures to improve growth and drug testing in neuroblastoma. Methods MOS™ were established from patient-derived tumoroids, patient-derived xenograft-derived fresh tumors and tumoroids, and a freshly dissociated patient tumor to compare growth and drug responses with suspension. Results Tumor cell growth in MOS™ was comparable or superior to suspension cultures. MOS™ drug screens were performed at a 2.5-fold lower seeding density compared to suspension, whilst maintaining reliable results with consistent drug sensitivity profiles and screen quality to suspension. Promisingly, drug testing in MOS™ was feasible within 9 days of receiving fresh PDX tumor tissue. Conclusion These results demonstrate in a proof-of-concept setting how MOS™ technology could support the establishment and drug screening of neuroblastoma cultures from low-input samples within clinically relevant timelines. MOS™ technology provides a promising functional platform to accelerate preclinical drug testing in neuroblastoma precision medicine.