Strategies for Epigenetically Reprogramming Neuroblastoma Cancer Stem Cells

High Risk neuroblastoma is the most common abdominal tumor in children and accounts for 15% of all pediatric cancer mortality. This is despite arduous intensive toxic chemotherapy treatments with major long-term side effects. Most deaths result from relapsed neuroblastoma, which grows back after initially responding to therapy. Thus, our major goal is to develop novel treatments to prevent neuroblastoma relapse. This will have a major impact on survival for neuroblastoma (currently less than 40% ).

It has become increasingly clear that cancer relapse is driven by special 'cancer stem cells'. Like normal non-malignant stem cells from the blood or other tissues, cancer stem cells self-renew and are resistant to drug treatments. Also like normal stem cells which generate multiple types of cells, 'cancer stem cells' remain immature and can generate all parts of a tumor at relapse. Exciting recent research shows that both 'normal' and 'cancer' stem cells share special mechanisms not found in non-stem cells to shut off and turn on essential 'stem cell' pathways. Incorporating new data from the stem cell field and cutting edge methods, we are investigating exactly how this process occurs in neuroblastoma.

This information is essential for the design of entirely new less toxic therapeutic approaches to specifically reverse or 'reprogram' these pathways. This should force cancer stem cells to evolve into non-malignant mature cells incapable of causing disease relapse. Our goal is to quickly translate our findings into the clinic for the young children suffering from this aggressive malignancy.