Patient-Derived 3D Models for Preclinical Drug Response Evaluation in Neuroblastoma

Abstract Background Neuroblastoma is the most common solid childhood tumor outside central nervous system. Metastatic and relapsed disease in neuroblastoma patients still has a poor prognosis. New treatment methods to improve therapy outcomes for with advanced are urgently needed. However, clinical trials currently only allow testing few substances even fewer patients. This increases need advance preclinical models preselect favorable candidates novel therapeutics. Aims study investigates advantages limitations of using bioreactor-based perfused 3D drug tumors exemplified neuroblastoma. Methods We established cell lines tissue slice-culture evaluated viability. Several inhibitors against hypoxia-related factors, associated progression, were tested including Aqb011 aquaporin 1 (AQP1) SLC-0111 carbonic-anhydrase IX (CAIX). Isothermal microcalorimetry was used measuring real time thermogenesis constructs. Results constructs presented similar morphological features compared cells intact featuring small, round blue cells. Perfused maintained its primary structure bioreactor up 10 days. Both responded inhibition significant decrease measured by microcalorimetry, if correlating hypoxic factor (AQP1 or CAXI) expressed. The AQP1 inhibitor CAIX heat production cultures. Conclusions newly establish two structure. Drug response monitoring can be applied these isothermal microcalorimetry. Monitoring times increased use bioreactor. Our an important first step preclinically evaluate new drugs patient-derived