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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Cancer Biology
First Advisor
Ana C. deCarvalho
Abstract
Glioblastoma (GBM) is the most aggressive adult type of glioma, a primary brain tumor. Furthermore, pediatric high-grade gliomas (HGG) are the deadliest childhood cancer. A combination of surgery, radiation, and chemotherapy has been used to treat glioma patients. Only one new therapy has been approved for treating glioma patients since 2005 despite only 17% of patients surviving longer than two years. Platelet derived growth factor receptor alpha (PDGFRA) is important for early brain development and both its expression and activity are altered in GBM patients. While PDGFRA inhibitors have been successful in limiting growth pre-clinically, PDGFRA inhibitors have not been effective in adult and pediatric clinical trials. Patient selection and drug toxicity are two of the reasons for the ineffectiveness of PDGFRA inhibitors. In at least 15% of GBM and HGG patients, PDGFRA is altered by increased gene copy number in amplified genomic regions. Our preliminary data demonstrates that PDGFRA amplification provides a growth advantage in patient-derived mouse models. The goal of this project is to (1) determine GBM tumor requirement for PDGFRA, (2) understand how the need for PDGFRA associates with PDGFRA amplification status, and (3) explain the importance of PDGFRA in the response of tumor cells to stressors such as therapy. In the short term, this will identify patients that respond to PDGFRA inhibitors. In showing that PDGFRA is essential for tumor growth, this will encourage drug developers to refocus on developing better PDGFRA inhibitors.
Recommended Citation
Berezovsky, Artem Dimitri, "Platelet Derived Growth Factor Receptor Alpha (pdgfra) Oncogene Dependency In Glioblastoma" (2023). Wayne State University Dissertations. 3940.
https://digitalcommons.wayne.edu/oa_dissertations/3940