Despite a tremendous effort in basic science, clinical trials, drug development, and technical advances in radiation oncology, glioblastoma remains incurable and improvements in overall survival have been marginal. While radiotherapy is one of the most effective treatment options for glioblastoma it cannot control the disease over time. This led us to conclude that novel combination therapies are desperately needed to improve radiation treatment outcome for patients suffering from this disease. The studies outlined in this proposal make are base on a hypothesis that is backed by our extensive preliminary data and published data in the literature. Specifically, that radiation causes a phenotype conversion of differentiated glioma cells into therapy-resistant glioma-initiating cells (GICs) and that interfering with this process will increase the efficiency of radiotherapy. The three aims of this study will address this aspect of glioma biology using an innovative tool to track GICs and their progeny and make use of unique resources and expertise available at UCLA. If successful, results from these studies and in particular Aim 2 and 3 will have wider impact on radiation oncology as these principles apply not only to glioblastoma but many other solid cancer.
This proposal will study possible reasons for radiotherapy failure in glioblastoma patients. It aims to understand how glioma stem cells escape radiotherapy and to uncover novel ways to improve the efficacy of radiation treatment for glioblastoma patients.
| Garrett, Matthew; Sperry, Jantzen; Braas, Daniel et al. (2018) Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities. Cancer Metab 6:4 |
| Duhachek-Muggy, Sara; Bhat, Kruttika; Vlashi, Erina et al. (2017) Growth Differentiation Factor 11 does not Mitigate the Lethal Effects of Total-Abdominal Irradiation. Radiat Res 188:469-475 |
| Qi, Xiangrong Sharon; Pajonk, Frank; McCloskey, Susan et al. (2017) Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation. Radiother Oncol 124:455-461 |
