Project 1: Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain Tumors
Basic Biological Sciences Co-Leader: Juan Fueyo, M.D.
Applied Sciences Co-Leader: Frederick F. Lang, M.D.
- Specific Aim 1: Determine the extent to which Delta-24-RGD can replicate in and spread through gliomas in situ in patients.
- Specific Aim 2: Determine the extent to which Delta-24-RGD and temozolomide are synergistic anti-glioma agents and examine the underlying mechanisms of the synergy.
- Specific Aim 3: Determine the extent to which bone marrow-derived human mesenchymal stem cells can improve the delivery of Delta-24-RGD to glioma.
Project 2: Targeting the PI3K Pathway in Gliomas with PI3K Inhibitors and Rational Combinations
Applied Sciences Co-Leader: W. K. Alfred Yung, M.D.
Basic Biological Sciences Co-Leader: Garth Powis, D.Phil.
Basic Biological Sciences Co-Leader: Oliver Bögler, Ph.D.
- Specific Aim 1: To study PX-866 and rational combinations in improved preclinical culture and animal models of glioma.
- Specific Aim 2: To initiate clinical trials of PX-866 and rational combinations.
- Specific Aim 3: To identify novel synergistic targets for rational drug combinations with PX-866 using siRNA synthetic lethality screening.
Project 3: Predicting Therapeutic Response in Glioblastoma and Targeting Refractory Tumors
Applied Sciences Co-Leader: Kenneth Aldape, M.D.
Applied Sciences Co-Leader: Howard Colman, M.D., Ph.D.
Basic Biological Sciences Co-Leader: Robert B. Jenkins, M.D., Ph.D.
- Aim 1: Evaluate the ability of a multi-gene panel to predict patient outcome (progression-free survival) in a retrospective sample of newly diagnosed GBM patients treated with standard therapy (TMZ-CR).
- Aim 2: Validate the multi-marker predictor in a prospective, randomized phase III trial of >800 patients (RTOG 05-25) and identify additional robust molecular profiles of refractory tumors.
- Aim 3: Utilize samples from clinical trials of newly diagnosed GBM to test the extent to which the multigene set is predictive of response to new targeted therapies.
Project 4: Genetic Modulation of Cognitive Function and Outcomes in Glioblastoma Patients
Basic Biological Sciences Co-Leader: Melissa L. Bondy, Ph.D.
Basic Biological Sciences Co-Leader: Christina A. Meyers, Ph.D.
Basic Biological Sciences Co-Leader: Margaret R. Wrensch, Ph.D.
Applied Sciences Co-Leader: Charles A. Conrad, M.D.
Applied Sciences Co-Leader: Susan M. Chang, M.D.
- Aim 1: To create a customized SNP chip (Golden Gate assay - Illumina platform) focusing on the neurocognitive, metabolizing, DNA repair and inflammation genes relevant to neurocognitive outcome.
- Aim 2: To conduct neurocognitive evaluations on all patients treated and followed at each institution following the standardized testing established for a number of collaborative group and pharmaceutical company sponsored studies.
- Aim 3: To integrate the data derived from Aims 1 and 2 to determine if variants in the neurocognitive, metabolizing, DNA repair and inflammation pathway genes alter the overall QOL.
- Core A: Administrative; Co-Directors: Oliver Bögler, Ph.D., and W.K. Alfred Yung, M.D.
- Core B: Pathology and Tissue Procurement; Co-Directors: Kenneth Aldape, M.D., and Gregory N. Fuller, M.D., Ph.D.
- Core C: Biostatistics; Director: Kenneth Hess, Ph.D.
- Core D: Clinical; Director: Mark R. Gilbert, M.D.
- Core E: Animal; Co-Directors: Frederick F. Lang, M.D., and Charles A. Conrad, M.D.