Funded Projects

Biorepository, Stem Cell Lines and Xenografts

Funding from the PBTF to the Biorepository Core provides for light microscopic and molecular analysis on all banked specimens in order that researchers have access to histologically and genotypically characterized tumor samples for diagnostic assessments in preclinical and clinical studies. In addition, funding supports ongoing development of pediatric brain tumor cell lines and patient-derived xenografts at Duke that enable the study of phenotypic and functional heterogeneity, the characterization of tumor subtypes, and preclinical drug testing. The resources of the core facilities are made available to researchers at Duke and other institutions.

• Award $300,000 over three years
• Principal Investigators Roger McLendon, MD and Stephen Keir, DrPH, Duke University
• Funding Partner The Kyrie Foundation

Cell Lines, Animal Models and Tumor Tissue Bank

Biospecimens obtained directly from the operating room during pediatric brain tumor resections are acquired, molecularly characterized and used to establish tumor cell lines and intracranial xenografts. These core resources, developed and maintained on an ongoing basis, are invaluable to help detect new therapeutic targets and to test novel therapies in animal models of the disease, guiding and improving future clinical therapies in pediatric brain tumor patients. The resources of the UCSF core facility are an essential component of the UCSF Brain Tumor Research Center. They are also made available to researchers at other institutions.

• Award $100,000 over three years
• Principal investigators Joanna Phillips, MD, PhD and Theodore Nicolaides, MD, University of California, San Francisco

Integrated Molecular and Clinical Characterization of Disseminated Pediatric Low-Grade Glioma: A Pediatric Low-Grade Glioma Task Force Initiative

Disseminated pediatric low-grade gliomas (dPLGGs) have been observed to exhibit distinct biologic behavior with some tumors appearing as upfront disseminated cystic solid tumors throughout the brain and spine, large single tumor with dissemination in the membrane surrounding the brain and spinal cord, or start as a single tumor which later disseminates to other parts of the brain and spine. This study aims to characterize the genetic alterations found in dPLGGs in view of these three clinically important subgroups using next-generation genomic technologies and correlate this with the clinical features and outcome of the disease. Identification of drivers of metastasis/dissemination will allow early identification of these aggressive tumors, facilitate risk stratification of newly diagnosed PLGGs and management of the disease.

• Award $197,550 over 1 year (2022-2023, PLGA Fund)
• Principal Investigators Dr. Michael Dewan, Monroe Carell Jr. Children’s Hospital at Vanderbilt and Drs. Cynthia Hawkins and Uri Tabori, The Hospital for Sick Children

Maintenance of DIPG Blood-Brain Barrier Integrity by Angiopoietin1

In order to enter brain tissue, molecules and cells in the circulation coursing through the central nervous system (CNS) must first cross a specialized biological border in blood vessel walls called the blood-brain barrier (BBB). Drug penetration across the BBB presents a fundamental challenge to effective treatment of many brain tumors, including diffuse intrinsic pontine gliomas (DIPGs), which are unresectable and only temporarily respond to radiation treatment. Through this Early Career Development grant, Dr. Phoenix will characterize the mechanisms that regulate Angiopoietin-1 (Angpt1) expression and function in DIPG and determine the potential of Angpt1-Tie2 inhibition to effect tumor-specific increases in BBB permeability and drug penetration. Findings will open the door for new approaches to manipulating the BBB in DIPG and ultimately better clinical outcomes for children.

• Award $300,000 over three years (Early Career Development Grant)
• Principal Investigator Timothy Phoenix, PhD, University of Cincinnati

Chromatin Immune Precipitation Sequencing

Much excitement in the low-grade astrocytoma field has been generated by the discovery of frequent mutations in a protein kinase known as BRAF. However, these BRAF mutations can account for only approximately one third of these pediatric tumors. Dr. Chuck Stiles and the PLGA program at Dana-Farber is focusing on genetic lesions that underlie the remaining two thirds of these tumors. Towards this end, this project’s researchers are creating a dedicated core facility for a technology known as Chromatin Immune Precipitation Sequencing ( ChIP/Seq). The ChIP/Seq method identifies potentially druggable genetic targets for DNA-binding proteins known as transcription factors. The ChIP method will be used to identify genetic targets for three transcription factors plus the Olig2 transcription factor which may play an even more pervasive role in pediatric LGAs.

• Principal Investigators Dr. Chuck Stiles, Dana Farber

Childhood Brain Tumor Tissue Consortium (CBTTC) Targets PLGA

This study at University of Texas M.D. Anderson Cancer Center, led by principal investigator Dr. Kwong-Kwok Wong, will investigate different methods to immortalize JPA primary cells which have limited growth potential.

• Principal Investigator Dr. Kwong-Kwok Wong, University of Texas M.D. Anderson Cancer Center

CBTN PLGG Working Group and Clinical Research Assistant

The Children’s Brain Tumor Network’s (CBTN) core efforts track longitudinal clinical data for all subjects. With 27% of all subjects enrolled with low-grade gliomas (LGG), CRCs at sites around the country spend 20% of their time tracking the clinical progress of LGG patients over the course of their journey. CBTN CRAs are tasked with obtaining consent from subjects and tracking their clinical data as well as reporting on the new data to the larger CBTN team.

• Award $64,000 over 1 year (2022-2023)
• Principal Investigators Dr. Adam Resnick, Children’s Hospital of Philadelphia

Analysis of BRAF in WHO Grade II Fibrillary Pediatric Astrocytomas

• Principal Investigator Charles G. Eberhart M.D., Ph.D., Peter Burger M.D. and Eli Bar Ph.D.

Prospective Assessment of Predictive/prognostic molecular biomarkers in the SIOP-LGG 201X adaptive phase III clinical trial

The principle aim of the trial is to identify the optimum treatment regimen with respect to efficacy, improvement of visual and neurological function, reduction of neurotoxicity as well as treatment duration using a randomized comparison of vinblastine (VBL) versus vincristine (VCR) in a carboplatin-based chemotherapy regimen, also randomizing 18 versus 12 months treatment duration.

• Award $428,000 over 2 years (2019 – 2021)
• Principal Investigators Dr. David Jones and Dr. Stefan Pfister, Heidelberg German Cancer Institute

PNOC021 Phase I Trial Evaluating the Combination of Trametinib and Everolimus in Pediatric and Young Adult Patients with Recurrent Gliomas

Although preclinical and clinical data support the use of single agent MEK or mTOR inhibitors in the treatment of pediatric LGGs, there are anecdotal reports of tumor progression or rapid regrowth following cessation of therapy. Development of tumor resistance to single-targeted agents is inevitable, one mechanism being upregulation of parallel pathways.

• Award $300,000 over 2 years (2020 – 2022)
• Principal Investigators Dr. Lindsay Kilburn, Children’s National Medical Center, Dr. Angela Waanders, Lurie Children’s Hospital of Chicago, Dr. Mohamed AbdelBaki, Nationwide Children’s Hospital