Childhood Cancer

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Investigating the regulation and role of DLL3 in Neuroblastoma

Institution: 
Children's Hospital of Philadelphia
Researcher(s): 
Gwyneth Shermanski
Grant Type: 
POST Program Grants
Year Awarded: 
2019
Type of Childhood Cancer: 
Neuroblastoma
Project Description: 

Mentor: Dr. John Maris

Neuroblastoma is a pediatric cancer that arises from dysregulation during nervous system development. Due to the developmental nature of the disease, these children are commonly diagnosed within the first year of life. The genetics of neuroblastoma tumors largely varies and contributes to the severity of the disease. For example, patients with unfavorable genetics are classified as high risk and have a five-year survival rate of less than 50%. Additionally,  survival after relapse is extremely rare, which underscores a need to develop effective treatment options for patients with high-risk neuroblastoma. New cancer treatment strategies include immunotherapy, which involves selectively delivering a chemotherapy agent to tumor cells based on cell-surface molecules that are expressed only on tumors. Some of the genetic changes that mark poor prognosis in neuroblastoma can upregulate certain cell-surface proteins. The Maris lab has identified several cell-surface proteins that are uniquely expressed on neuroblastoma cells. One of these proteins is delta-like 3 (DLL3), which inhibits a well-studied cell signaling pathway. DLL3-targeted immunotherapies are currently being investigated in other adult cancers, including neuroendocrine and small cell lung cancers. This immunotherapy has also shown promise in eliminating neuroblastoma tumors in mouse models, however, the role of the DLL3 protein at the cell surface and the cause of overexpression in neuroblastoma are currently unclear. We will investigate the genetic events that contribute to high DLL3 expression and evaluate the signaling pathways associated with DLL3 on the surface.