Biomarker, Bioinformatics and Biorepository Core

PROJECT SUMMARY – Biomarker, Bioinformatics and Biorepository Core The Duke/UT Southwestern Glioblastoma Therapeutics Network (GTN) team will complete pre-clinical development of a novel treatment (6-thio-dG) for patients with glioblastoma (GBM) and investigate its biologic activity in an early-phase clinical trial. This Biomarker, Bioinformatics and Biorepository Core (Bio-MIR Core) will

support this mission by 1) providing logistical, biomarker, biostatistical, bioinformatic and biorepository support that enables this GTN team’s investigators to optimize 6-thio-dG treatment for patients with GBM, and 2) serving as a resource to other GTN sites by enabling the broader network to access the same expertise and tissues.

The Bio-MIR Core will be indispensable for the successful conduct of the studies proposed in this application, including the early-phase clinical trial of 6-thio-dG, by standardizing protocols for the collection of tissues and centralizing analyses of key biomarkers of patient eligibility and tumor response to 6-thio-dG treatment (Aim 1).

We will provide expert neuropathologic consultation through central review of previously resected tumors and ascertain IDH1/2 and TERT-promoter mutation status using CLIA-approved assays to determine eligibility to receive 6-thio-dG. Following 6-thio-dG treatment and tumor resection, the Bio-MIR Core will again oversee

central neuropathologic review and measure pharmacodynamic endpoints, including γH2AX measures of DNA damage (primary trial endpoint). The Bio-MIR Core will provide biobanking services for the collection, processing and storage of all GBM patient tissues in a CAP-certified setting, and distribute these tissues both within the

Duke/UTSW GTN and across all GTN sites (Aim 2). The Bio-MIR Core will also provide biostatistics and bioinformatics expertise for the conduct, analysis, and reporting of correlative studies, and ensure data integrity through centralized integration of clinical data, including multi-platform data integration and coordination (Aim 3).

Further, the Bio-MIR Core will promote an exemplary research culture wherein best data management practices are used throughout to ensure data integrity, provenance, security, and reproducibility of study findings. The Bio- MIR Core will benefit from institutional and NIH investments made in key shared resources, including clinical

data warehousing and multi-institutional biobanking and specimen sharing, and utilize the expertise of investigators that have conducted multi-center GBM research for more than three decades. The Bio-MIR Core will facilitate collaboration between GTN investigators and will also work with the designated Network

Coordination Center for trans-GTN sharing of resources and participation in clinical trials of therapies advanced by the GTN Steering Committee to multi-center evaluations. In this manner, the Bio-MIR Core will serve as an indispensable resource helping to achieve the GTN’s overall goal of developing novel, effective agents that can

cross the blood-brain-barrier and testing them in the clinic to improve treatment for adults with GBM.