Childhood Cancer

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Targeting SHP2 in Receptor Tyrosine Kinase-driven Neuroblastomas

University of Pennsylvania
Sabina London
Grant Type: 
POST Program Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Each year, 700 children are diagnosed with neuroblastoma in the United States. Tumors emerge in the sympathetic nervous system, most commonly in the adrenal glands. We are particularly focused on high-risk neuroblastoma, where 50% of young children have a fatal disease despite intensive upfront therapy. We and others have shown that in 14% of high-risk neuroblastoma patients, mutations in the anaplastic lymphoma kinase (ALK) oncogene are essential for the progression of neuroblastoma. ALK is a receptor tyrosine kinase that is crucial for cell signaling and turning off this oncogene turns out to be quite challenging. The exact mechanisms of how ALK signals in the context of neuroblastoma remains unknown. Studies have shown that the protein called Src homology region 2-containing protein tyrosine phosphatase (SHP2) is important in the signaling of other cancers that rely on receptor tyrosine kinases that activate critical cell signaling pathways and allow for the survival of cancer cells, such as non-small cell lung carcinoma. Preliminary data in our lab has shown that inactivating ALK can lead to down-regulation of the active form of SHP2 and could slow down or turn off tumor growth. Therefore, we hypothesize that SHP2 functions as a downstream effector of ALK. 

Project Goal
The objective of my project is to determine if the SHP2 protein contributes to survival in ALK-driven neuroblastoma tumors. We hypothesize that SHP2 inhibition leads to decreased proliferation of neuroblastoma cells. We will analyze the changes in protein expression of known effectors of SHP2 as well as assess growth kinetics and viability of the cells with a new HP2 inhibitor we have in the lab. The overall goal of this project is to determine if SHP2 could be a therapeutic target in neuroblastoma.

Mentored by Dr. Yael Mossé
Children’s Hospital of Philadelphia, Philadelphia, PA

Co-funded by: 
Northwestern Mutual Foundation