The most common treatment for newly diagnosed glioblastoma (GBM) is surgical debulking of tumor followed by radiation therapy (RT) and chemotherapy with the DNA alkylator temozolomide (TMZ). Average survival for GBM patients treated in this manner is approximately 15 months, which is a time during which their tumor will recur, and no treatment has been identified that significantly improves the survival of patients with recurrent tumor. A central hypothesis associated with the studies proposed herein is that RT + TMZ therapy causes mutations in GBM, and that improved treatment of recurrent GBM requires a detailed understanding of these mutations. The research associated with this proposal will generate, characterize, and validate recurrent RT modified, TMZ modified, and RT + TMZ modified GBM tumor models that can be used by the principal investigator and others interested in the study and treatment of recurrent GBM.
Patients with glioblastoma (GBM), the most common and malignant primary brain tumor in adults, are routinely treated with radiation therapy (RT) and the chemotherapeutic temozolomide (TMZ), because this therapeutic combination is known to extend survival of GBM patients. However, all GBM recur, and at recurrence RT + TMZ-treated tumors are known to be therapy resistant and especially aggressive. This project will increase understanding of how RT + TMZ change GBM and contribute to tumor aggressiveness at recurrence, and it will also generate sustainable recurrent GBM resources that will be shared with others to motivate increased research activity leading to improved treatment of recurrent GBM.
| (2017) Correction: Dedifferentiation of Glioma Cells to Glioma Stem-like Cells By Therapeutic Stress-induced HIF Signaling in the Recurrent GBM Model. Mol Cancer Ther 16:1199 |
| Wainwright, Derek A; Horbinski, Craig M; Hashizume, Rintaro et al. (2017) Therapeutic Hypothesis Testing With Rodent Brain Tumor Models. Neurotherapeutics 14:385-392 |
| Lee, Gina; Auffinger, Brenda; Guo, Donna et al. (2016) Dedifferentiation of Glioma Cells to Glioma Stem-like Cells By Therapeutic Stress-induced HIF Signaling in the Recurrent GBM Model. Mol Cancer Ther 15:3064-3076 |
