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Pediatric Oncology Branch Home > Scientific Programs > Cell & Molecular Biology Section

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Cell & Molecular Biology Section

Every year approximately 700 cases of Neuroblastoma and 210 cases of Ewings’ sarcoma are diagnosed in children less than twenty years of age. Half will fail conventional therapy. Despite the progress made in the development of clinical/genetic based staging systems for Neuroblastoma and Ewings’ sarcoma the prognosis for patients with unfavorable disease remains dismal. The focus of the Cell & Molecular Biology Section has been to develop a comprehensive understanding of the biology of peripheral neuroectodermal tumors cells. We do so by developing in vitro and in vivo modeling systems that will enable genetic interrogation of the biologic systems of tumor cells and their normal counterparts. The insights gained from these studies serve as a platform for the development of novel therapies for the treatment of children with these diseases.

A number of genetic alterations have been identified in Neuroblastoma tumors which are thought to contribute to tumorigenicity. Despite these genetic alterations, retinoids (derivatives of Vitamin A) are capable of arresting cell growth, inducing differentiation and suppressing tumorigenicity. Thus by activating alternative intracellular signaling programs we may be able to bypass genetic defects and restore growth control and induction of differentiation.

Project I: The BDNF/TrkB pathway is important in the survival and metastatic capability of Neuroblastoma tumor cells. The specific aims are;

1. To identify and characterize the molecular mechanisms mediating these processes
2. To evaluate the therapeutic potential of targeting downstream signaling intermediaries of the BDNF/TrkB pathway.

Project II: Clinical, histopathologic and genetic evidence indicates that alterations in the regulation of normal development contributes to Neuroblastoma tumorigenesis. The specific aims are;

1. To identify and characterize Neuroblastoma tumor intiating cells/cancer stem cells.
2. To study signal transduction pathways regulating neuroblastoma differentiation.
3. To identify key differentiation genes, such as CASZ1 that regulate differencetion/developmental programs.

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