Off-campus WSU users: To download campus access dissertations, please use the following link to log into our proxy server with your WSU access ID and password, then click the "Off-campus Download" button below.

Non-WSU users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

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.

Off-campus Download

Share

COinS