Five Scientific Cores
The goal of the Preclinical Trials Core is to assess the efficacy and safety of novel drug cocktails that have never been tested before for glioblastoma in animal models. The core utilizes patient-derived xenograft models to test the drug combinations which recapitulate the heterogeneous and complex nature of human glioblastoma tumors.
- Xenograft animal modeling
- Transgenic animal modeling
- Animal toxicology
- Drug resistance modeling
- Combinatorial therapy validation
Any new drug under consideration at the Ivy Brain Tumor Center is first vetted by the Pharmacokinetics (PK) Core for its brain penetration properties under preclinical settings. The lab develops and validates assays for each drug through complex processing using the LC-MS and HPLC system. Drugs with the best pharmacokinetic profiles are progressed into our Phase 0 clinical trials. Once patients receive the drug and undergo surgery, the tumor tissue is analyzed in a CAP/CLIA certified laboratory for the levels of free drug within the tumor tissue. Patients whose tumors have high levels of the free drug continue to receive the drug at a therapeutic dose. The PK lab at the Ivy Brain Tumor Center is one of the first CAP/CLIA certified laboratories to analyze effective drug concentrations that reach brain tumors.
- CNS Penetration Modeling
- Animal Study Pharmacokinetics
- Human Trial Pharmacokinetics
- Medicinal Chemistry
The Pharmacodynamics (PD) Core identifies, designs and validates assays/biomarkers for patient enrollment into Phase 0 trials and to assess target modulation after drug treatment. The laboratory employs the Gene Reader platform and a brain tumor-specific IvySeq gene panel to identify genetic mutations in tumor samples and a fully automated Leica BOND system to perform immunohistochemistry assays. The validated assays are utilized to compare changes in target levels between the archival tissue and tumor tissue after drug treatment in a CAP/CLIA certified laboratory. The PD Core at the Ivy Brain Tumor Center is one of the few laboratories that examine direct target modulation after drug treatment.
- Mechanism of Action Modeling
- Assay Development and Validation
- Animal Study Pharmacodynamics
- Human Trial Pharmacodynamics
- Human Trial Tissue Management
The Physiologic Imaging Core establishes and optimizes state-of-the-art image acquisition and analysis methods that are leveraged at each stage of our Phase 0 trials. The core uses conventional and advanced image-based biomarkers to inform surgical localization of samples collected for pathologic, molecular, genetic, and PK/PD evaluation. Quantitative imaging techniques enable interrogation of blood-brain barrier integrity and prediction of regional drug pharmacokinetics. For patients who progress to a Phase 2 trial, the core uses image-based biomarkers for robust and early evaluation of therapy response.
- Preclinical Tumor Surveillance
- Clinical Tumor Surveillance
- Non-Invasive Pharmacokinetics
- Blood-Brain Barrier Quantification
- Radiolabeled Drug Tracking
The Ivy Brain Tumor Center’s Bioinformatics Core will play a critical role in providing the necessary infrastructure to calculate and analyze the incredible amount of data generated by the Ivy Brain Tumor Center.
- High-Throughput Infrastructure
- Exome Data Analysis
- Genome Data Analysis
- Transcriptome Data Analysis
- DNA Methylation Data Analysis