Neuroblastoma, an embryonal tumor arising from precursor cells of the sympathetic nervous system, is the most common extracranial solid tumor in children and accounts for 15% of cancer-related deaths in this population. Neuroblastomas are characterized by highly heterogeneous clinical behavior, ranging from spontaneous regression to aggressive metastatic disease. In high-risk neuroblastoma patients, the five-year survival rate is only 50%. The limited efficacy of current treatment approaches and their high toxicity underscores the need for novel and more targeted therapies.

Two promising targeted therapies are idasanutlin and dinutuximab. In my project proposal, I aim to investigate the effects of idasanutlin and dinutuximab on the various cell types present within a neuroblastoma tumor. By gaining a deeper understanding of why certain (tumor) cells respond—or fail to respond—to a therapy, (combination) therapies can be better optimized.

For this project, I will utilize neuroblastoma mouse models treated with either idasanutlin or dinutuximab, followed by RNA-based spatial transcriptomics (a technology enabling detailed molecular characterization of the transcriptome while preserving spatial information) and liquid biopsies (a technology that, in this case, characterizes tumor RNA present in blood plasma) to map tumor heterogeneity and tumor responses. I anticipate that a better understanding of these treatment mechanisms and a more precise characterization of the tumors will lead to improved or novel combination therapies.