Research
The Neuro-Oncology Program studies brain tumors, with a focus on three main areas of research.
Brain tumor biology: Identifying pathogenic and tumor biology factors that lead to brain tumor initiation and progression
Our advances in this research area include:
- Demonstrating that variants that influence telomere length near TERT and TERC are associated with high-grade glioma
- Demonstrating that molecularly grouping patients with glioma based on 1p/19q, IDH and TERT promoter mutations defined highly clinically relevant prognostic groupings
- Demonstrating that the mitotic kinesin KIF11 is a driver of invasion, proliferation and self-renewal in glioblastoma
- Evaluating the role of SGEF in regulating TWEAK/Fn14/NF-κB signaling and in promoting survival by modulation of the DNA repair response to temozolomide
Biomarkers: Identifying and assessing laboratory and imaging biomarkers to diagnose brain tumors and to determine prognosis and predict response to therapy
Our advances in this research area include:
- Pioneering the use of deep machine learning to analyze MRI features, including demonstrating that deep machine learning can be used to automatically segment MR images and to identify an MR imaging signature predictive of MGMT promoter methylation status
- Developing radio-genomic predictors of genetic alterations and demonstrating that MRI texture analysis could be used to identify tumors with EGFR and/or PDGFRA amplification
- Characterizing FDOPA PET imaging as an improved targeting strategy for surgical and radiotherapy planning for gliomas
- Providing the basis for BISQFP funding supporting MGMT promoter methylation as a predictive biomarker in the Alliance for Clinical Trials in Oncology A071102 randomized Phase II/III clinical trial, which became the first example of a clinical predictive biomarker being defined a priori in a patient-derived xenograft preclinical trial
Novel therapeutic strategies: Developing new interventions that improve response rates and overall survival, reduce symptoms, and improve quality of life
Our advances in this research area include:
- Demonstrating similar survival but significantly reduced neuro-cognitive deficits for patients treated with stereotactic radiation compared with whole-brain radiation
- Demonstrating the benefit of memantine to prevent neuro-cognitive decline in patients receiving whole-brain radiation
- Demonstrating that PCV chemotherapy significantly extends survival in low-grade gliomas
- Demonstrating that immunovirotherapy with measles virus strains in combination with anti-PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment
- Identifying a signature of molecular features associated with optimal infectivity of measles in the development of measles virotherapy
- Determining no improvement in outcome for patients with recurrent glioblastoma treated with a combination of bevacizumab and sorafenib compared with patients treated with bevacizumab alone
- Performing preclinical studies to support a rationale to develop the MC1272 clinical trial, Allogeneic Tumor Lysate-Pulsed Autologous Dendritic Cell Vaccination in Newly Diagnosed Glioblastoma
- Helping evaluate a novel heat-shock protein vaccine for recurrent glioblastoma
- Leading the MC1572 Phase II clinical trial evaluating the PD1 inhibitor pembrolizumab in combination with radiation and chemotherapy for newly diagnosed glioblastoma
- Evaluating the importance of drug distribution across the blood-brain barrier within gliomas and other brain tumors
- Demonstrating that veliparib enhances the efficacy of TMZ in tumors with MGMT promoter hypermethylation
- Demonstrating that combining everolimus with conventional chemoradiation had moderate toxicity and no appreciable survival benefit compared with conventional therapy
- Demonstrating that limited distribution to brain tumors may limit the efficacy of the Wee1 inhibitor MK-1775 in glioblastoma