Active project

Joshua Breunig, PhD

Wake Forest University

Pre-clinical Testing of a Targeted Metabolic Therapeutic for G34R Glioma

Dr. Breunig’s team is testing a metabolic treatment strategy for G34R-mutant pediatric glioma, an aggressive brain tumor with few effective options. His work targets the tumor’s dependence on the amino acid arginine and is generating the evidence needed to support clinical testing in children and young adults.

CureSearch Acceleration Initiative Award

2024 · Pediatric glioma

Project Overview About the Researcher Research Updates

Pediatric brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children 18 and under. Current therapies have a high risk of brain injury and serious long-term effects, illustrating the dire need for the development of safer, more effective treatments. However, development of newer and safer treatments is challenging due to the lack of relevant disease models in which to test their effectiveness.

Joshua Breunig, PhD, is a CureSearch Acceleration Initiative Awardee at Cedars-Sinai in Los Angeles aiming to change the treatment landscape for children with brain tumors. Specifically, his work focuses on G34R-mutant pediatric diffuse glioma, an incurable brain tumor that develops in children and young adults. Dr. Breunig has developed a novel modeling system called MADR (Mosaic Analysis with Dual Recombinases), which allows for the creation of “personalized” brain tumor models down to the single cell level. Using MADR, Dr. Breunig has uncovered a key vulnerability in these tumors – the inability of the tumor to create the amino acid arginine, making it reliant on other sources of arginine for survival.

Arginine deiminase is an enzyme that converts arginine into citrulline and can be used to deprive tumor cells of their access to arginine, hindering their growth and promoting rapid cell death. ADI-PEG 20 is a version of this enzyme that is already in use in clinical trials, including for adult brain tumors, with a strong safety profile. In his CureSearch-funded work, Dr. Breunig proposes to use the MADR modeling platform along with matched human pediatric glioma tumor cell lines to test ADI-PEG 20 as a targeted therapeutic for pediatric glioma in combination with standard-of-care treatment. He believes that this approach will hinder tumor growth and lead to anti-tumor toxicity. Furthermore, the results of this study will lay the foundation for use of ADI-PEG 20 in clinical trials in pediatric patients, which are actively being planned, potentially leading to a new treatment option and increased survival for children affected with G34R-mutant glioma.

This Award comes at the perfect time in that it will enable our collaborative team to rapidly translate our discovery of this metabolic vulnerability into an optimized clinical trial by exploiting evidence-based pre-clinical experimentation. – Dr. Joshua Breunig

Project at a glance

Program: Acceleration Initiative Award
Institution: Wake Forest University
Focus: Pediatric glioma

Joshua Breunig, PhD

Dr. Breunig, PhD is an Associate Professor of Biomedical Sciences and the Director of the Confocal Microscopy Core at Cedars-Sinai in Los Angeles, California. The lab of Joshua Breunig investigates the molecular controls of neural stem cell behavior in the brain, specifically exploring the signaling pathways governing the differentiation of stem cells into neurons and glia.

Follow the project’s progress.

Research Update — June 2026

Dr. Breunig and his team continue to generate strong evidence supporting ADI-PEG20 as a potential new treatment for children and young adults with G34R-mutant glioma and other high-grade gliomas.

Over the past six months, they completed a series of preclinical studies in both mouse models and advanced human tumor organoid models that consistently demonstrated the greatest therapeutic benefit when ADI-PEG20 was combined with radiation therapy. These findings further strengthen the rationale for targeting the tumor’s dependence on arginine and support the use of ADI-PEG20 alongside standard treatments.

Importantly, the team has reached a major translational milestone with the advancement of PNOC034, the first clinical trial to evaluate ADI-PEG20 in children and young adults with newly diagnosed high-grade glioma. The trial has received key regulatory approvals, including FDA authorization, and is expected to begin enrolling patients in July 2026. With plans to enroll approximately 97 patients, including a dedicated cohort of children with G34R-mutant glioma, this study represents a significant step toward bringing a promising new treatment option to patients while highlighting the direct clinical impact of the preclinical research supported by CureSearch.