The Identification of Neuroblastoma Cancer Stem Cells.

Neuroblastoma is one of the most common cancers in children, only leukemias and brain cancers are more frequent. The five-year survival for children with metastatic neuroblastoma is only 35%. With recurrent disease, this percentage is even lower. In addition, all modalities currently used in treating cancers including chemotherapy, radiation, and surgery are utilized in these patients. For a four year old, this can encompass a large portion of his or her short life. This is a disease that medicine must have greater success with in the future. Our laboratory has identified cancer stem cells in human and mouse breast cancer and we now propose studying neuroblastoma. The cancer stem cell theory states that not all parenchyma of the tumor has the ability to form tumor implying that the tumor is heterogeneous. Cancer stem cells are a specific subpopulation, often a small minority of cells, that have the ability to self-renew, give rise to more differentiated progeny, and is under genetic control by which proper ratios of cell types are maintained. In this model, tumors are aberrant caricatures of their normal organ counterparts. And if cancer stem cells share characteristics with other stem cells, they may also be in resting phase more often enabling them to be more chemoresistant. Our central hypothesis is that neuroblastoma has a cancer stem cell compartment responsible for the propagation, metastasis, and relapse of the tumor.