Glioblastoma (WHO grade IV astrocytoma; GBM) is the most common and deadly primary malignant brain tumor in adults. Therapy development has been hampered by the heterogeneous nature of GBM. Within GBM, a subset of tumor cells known as brain tumor initiating cells (BTICs) are highly tumorigenic and have some properties of neural stem cells. By co-opting the high affinity neuronal glucose transporter type 3 (GLUT3) brain tumor initiating cells (BTICs) can preferentially survive in low nutrient tumor microenvironments; leading to tumor promotion and progression. GLUT3 expression in many solid tumor types such as GBM, colon cancer, head and neck cancers and ovarian cancer is correlated with poor prognosis and survival. High GLUT3 expression also correlates with metastatic or invasive disease. The relationship between GLUT3 expression and invasion in GBM has not been explored. In this study, we aim to understand the role of metabolic reprogramming by GLUT3 in the invasion of GBM and explore opportunities for the pharmacological targeting of GLUT3 . We have identified novel GLUT3 inhibitors that are able to preferentially inhibit the growth and glucose up take of BTICs with little toxicity to non-neoplastic cells. Through this study, we hope to understand the role of GLUT3 in tumors and to identify a potential new therapeutic option to target metabolic reprogramming for the treatment of GBM.

Public Health Relevance

/ RELEVANCE Metabolic reprogramming is an emerging hallmark of cancer. We have determined that glucose transporter 3 plays a main role in the metabolism of glioblastoma derived brain tumor initiating cells. Understanding the consequences of and targeting GLUT3 shows promise for improving the treatment of glioblastoma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS105458-02
Application #
9812767
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Fountain, Jane W
Project Start
2018-08-01
Project End
2021-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294