Our research is focused on neuroblastoma, a childhood tumor originating from the sympathetic nervous system. Children with aggressive neuroblastoma have poor survival rate despite intense treatment. The overall aim of our research is to identify new treatment targets for aggressive neuroblastoma. In various cancers, a subpopulation of cancer cells with a particular immature phenotype – known as cancer stem cells – are often treatment resistant. One of our research objectives is to isolate and characterize cancer stem cells in neuroblastoma in order to find molecular drivers of this phenotype that would allow us to successively target this particular subgroup. We are isolating tumor cells from neuroblastoma patient derived xenografts (PDXs) and culture them as tumor spheres under stem cell promoting conditions in order to retain a stem cell like phenotype. Previous results from our group have depicted hypoxia-inducible factor 2α (HIF-2α) as a potential marker for neuroblastoma stem cells. HIF-2α is part of a transcription factor that is stabilized during hypoxia (low oxygen pressure). Hypoxia is common in all solid tumor forms and promotes tumor aggressiveness and drug resistance. Thus, tumor hypoxia correlates with poor clinical outcome in many cancers. Our second research aim is to determine the role of HIF-2α in tumor-initiation, metastasis and drug resistance in neuroblastoma.
Cancer and Oncology Neuroblastoma, hypoxia, cancer stem cells