This Duke Brain Tumor SPORE grant consists of four projects, five cores, a Developmental Research Program, and a Career Development Program. The goal of the proposed research is to advance knowledge of brain tumor biology and etiology and to translate these into clinical protocols that represent significant and novel advances in the management of these therapeutically intractable tumors. The grant, as a whole, and each project and core, are led by basic and clinical Principal Investigators. In Project 1, novel therapeutics that target the GSTP1 protein, overexpressed and a poor prognostic indicator in malignant gliomas, will be rationally developed and evaluated for clinical efficacy. Project 2 will investigate novel molecular mechanisms of resistance of CNS tumors to Temodar, a clinically active brain tumor agent and evaluate the clinical efficacy of a PARP inhibitor in reversing Temodar resistance. Project 3 will investigate dendritic cell-based vaccination against CMV as a therapeutic modality in malignant glioma and the underlying mechanisms of the anti-tumor response. In Project 4, molecular and epidemiologic studies will examine the etiology of brain tumors in a case-control study. Exposure to putative neurocarcinogens will be examined and polymorphisms in metabolism and DNA repair genes will be examined as a determinant of brain tumor risk and treatment-associated toxicity. The cores include a Tissue Procurement and Genetics Core, an Investigational New Drug Permit Core, a Phase I/II Clinical Trials Core, a Biostatistics and Information Systems Core, and an Administrative Core which will provide critical infrastructural and service functions. The Developmental Research Program will consist of pilot projects identified from the entire Cancer Center membership at Duke as well as from selected, outside institutions. Emphasis is on investigators who have not previously worked in neuro-oncology. Nine examples of pilot projects from senior investigators at Duke who have not previously worked on brain tumors are included.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA108786-05S1
Application #
7847314
Study Section
Special Emphasis Panel (ZCA1-GRB-V (M1))
Program Officer
Arnold, Julia T
Project Start
2009-06-01
Project End
2010-07-31
Budget Start
2009-06-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$25,969
Indirect Cost
Name
Duke University
Department
Pathology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Kurmasheva, Raushan T; Kurmashev, Dias; Reynolds, C Patrick et al. (2018) Initial testing (stage 1) of M6620 (formerly VX-970), a novel ATR inhibitor, alone and combined with cisplatin and melphalan, by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 65:
Lock, Richard; Carol, Hernan; Maris, John M et al. (2017) Initial testing (stage 1) of the curaxin CBL0137 by the pediatric preclinical testing program. Pediatr Blood Cancer 64:
Kurmasheva, Raushan T; Sammons, Melissa; Favours, Edward et al. (2017) Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 64:
Kurmasheva, Raushan T; Gorlick, Richard; Kolb, E Anders et al. (2017) Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 64:
Attiyeh, Edward F; Maris, John M; Lock, Richard et al. (2016) Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. Pediatr Blood Cancer 63:276-86
Gorlick, Richard; Kolb, E Anders; Keir, Stephen T et al. (2016) Initial Testing of NSC 750854, a Novel Purine Analog, Against Pediatric Tumor Models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 63:443-50
Kang, Min H; Reynolds, C Patrick; Kolb, E Anders et al. (2016) Initial Testing (Stage 1) of MK-8242-A Novel MDM2 Inhibitor-by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 63:1744-52
Nair, Smita K; Driscoll, Timothy; Boczkowski, David et al. (2015) Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma. J Neurooncol 125:65-74
Carol, Hernan; Fan, Mannie M Y; Harasym, Troy O et al. (2015) Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 62:65-71
Okamura, Tatsunori; Antoun, Gamil; Keir, Stephen T et al. (2015) Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells. J Biol Chem 290:30866-78

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