Glioblastoma is the most common malignant brain tumor of adults and is among the most lethal of all cancers. Deregulation of the PI3K/Akt pathway signaling, which promotes malignant transformation, tumor progression and radiation-resistance in pre-clinical models, is common in glioblastomas. However, its impact on glioblastoma patient survival and response to therapy is not known. Determining the effect of deregulated PI3K pathway signaling on glioblastoma patient survival and response to therapy may potentially translate directly into improved therapy for glioblastoma patients, particularly in light of the availability of specific PI3K signaling pathway specific inhibitors. This proposal brings together the powerful resources of an NCI sponsored multi-institutional cooperative group, the Radiation Therapy Oncology Group (RTOG), with its meticulously characterized clinical samples, and a team of investigators that has demonstrated ability to analyze the activation state of the PI3K pathway in glioblastoma patient samples. This proposal is an important extension of these studies, and it takes full advantage of this important NCI-sponsored resource.
The specific aims of this proposal are:
Aim 1 : We will determine whether activation of the PI3K pathway is associated with diminished survival of glioblastoma patients.
Aim 2 : We will determine whether activation of the PI3K pathway is associated with radiation resistance in glioblastoma patients.
Aim 3 : We will identify molecular features of glioblastomas that underlie response to EGFR, mTOR and farnesyl transferase inhibitors under investigation in ongoing and planned RTOG trials to optimize delivery and identify patients who will derive greatest benefit from these biotherapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA108633-05
Application #
7595195
Study Section
Special Emphasis Panel (ZRG1-DT (01))
Program Officer
Bernhard, Eric J
Project Start
2005-05-01
Project End
2011-03-31
Budget Start
2009-09-22
Budget End
2011-03-31
Support Year
5
Fiscal Year
2009
Total Cost
$464,424
Indirect Cost
Name
Ohio State University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Palanichamy, Kamalakannan; Kanji, Suman; Gordon, Nicolaus et al. (2017) NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability. Clin Cancer Res 23:2325-2334
Chang, Susan M; Chakavarti, Arnab; Bell, Erica H (2017) Reply to letter on results of NRG Oncology RTOG 9813. Neuro Oncol 19:739
Bell, Erica Hlavin; Pugh, Stephanie L; McElroy, Joseph P et al. (2017) Molecular-Based Recursive Partitioning Analysis Model for Glioblastoma in the Temozolomide Era: A Correlative Analysis Based on NRG Oncology RTOG 0525. JAMA Oncol 3:784-792
Beyer, Sasha; Fleming, Jessica; Meng, Wei et al. (2017) The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas. Cancers (Basel) 9:
Palanichamy, Kamalakannan; Thirumoorthy, Krishnan; Kanji, Suman et al. (2016) Methionine and Kynurenine Activate Oncogenic Kinases in Glioblastoma, and Methionine Deprivation Compromises Proliferation. Clin Cancer Res 22:3513-23
Buckner, Jan C; Shaw, Edward G; Pugh, Stephanie L et al. (2016) Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med 374:1344-55
Bell, Erica Hlavin; Chakraborty, Arup R; Mo, Xiaokui et al. (2016) SMARCA4/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non-Small Cell Lung Cancer. Clin Cancer Res 22:2396-404
Singh, Mamata; Leasure, Justin M; Chronowski, Christopher et al. (2014) FANCD2 is a potential therapeutic target and biomarker in alveolar rhabdomyosarcoma harboring the PAX3-FOXO1 fusion gene. Clin Cancer Res 20:3884-95
Juratli, Tareq A; Engellandt, Kay; Lautenschlaeger, Tim et al. (2013) Is there pseudoprogression in secondary glioblastomas? Int J Radiat Oncol Biol Phys 87:1094-9
Chakravarti, Arnab; Wang, Meihua; Robins, H Ian et al. (2013) RTOG 0211: a phase 1/2 study of radiation therapy with concurrent gefitinib for newly diagnosed glioblastoma patients. Int J Radiat Oncol Biol Phys 85:1206-11

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