Duke University’s Reitman Lab recently celebrated the publication of their first study based on original research started and finished in the lab. The lab is led by Dr. Zachary James Reitman, an Assistant Professor of Radiation Oncology, Pathology and Neurosurgery, a Duke Cancer Institute member, and the recipient of an Early Career Development grant from the Pediatric Brain Tumor Foundation.

The Pediatric Brain Tumor Foundation’s Early Career Development program supports rising stars in research, like Dr. Reitman, who are working on the next breakthrough in pediatric brain cancer treatment. Given the significant and ever-increasing challenges faced by junior investigators in establishing successful research programs, these multi-year research grants provide recipients the funding needed to become fully independent investigators. Equally importantly, our scientific advisors provide invaluable mentorship as grantees pursue advancements and novel therapies for children with brain tumors.

Dr. Reitman received a three-year, $300,000 Early Career Development grant, and the paper resulting from this funding is a significant milestone in his career: his first publication of new, original data and the first to list him as the corresponding author.

Published in Cancers, the study explores how radiation therapy in a PTEN-mutated brainstem glioma is affected by inhibiting the function of ataxia–telangiectasia mutated kinase (ATM), a master regulator of the cellular response to radiation therapy. The current standard of care for brainstem gliomas is radiation therapy, but these deadly tumors inevitably progress at some point after treatment. One treatment strategy for brainstem gliomas under preclinical investigation involves inactivating ATM. While ATM inactivation makes some tumors more sensitive to radiation therapy, this sensitivity may depend on the genetic makeup of the tumor.

The research team developed a genetically engineered mouse model of a PTEN-mutated brainstem glioma and used genetic tools to test whether ATM inactivation affected this important tumor subtype’s radiosensitivity. The team found that inactivation did not enhance the efficacy of radiation therapy in the mouse models, which indicates that PTEN mutational status should be considered in the design of inclusion criteria and correlative studies for future clinical trials studying ATM inhibitors in brainstem glioma patients.

“The Pediatric Brain Tumor Foundation’s support helped us carry out this study, which is the first major publication from our new lab at Duke,” says Dr. Reitman. “The results will guide clinical trial design for children with brain tumors, and this article shows that our group can carry out the genetically engineered mouse work and complex radiation therapy work needed for future studies of pediatric brain tumors.”

Earlier this year, the Pediatric Brain Tumor Foundation awarded Dr. Reitman a new grant for his project, Data Project Investigating High-Grade Giloma Immune Microenvironment During Tumorigenesis and Treatment in Primary Mouse Models. This additional funding will generate ideal preliminary data to show that the project team at Duke has single-nucleus and spatial RNA-sequencing data on their mouse models, providing “anchor data” that can be used to compare these models with human tumors and identify gene signatures to test when the mice are exposed to different therapies.

The milestone publication of Dr. Reitman’s paper and his new project’s demonstration of the mouse models’ feasibility and characterization will greatly enhance future grant submissions to the National Cancer Institute, the largest funder of cancer research in the world. Because the NCI’s multi-million-dollar grants are highly competitive, scientists studying childhood brain cancer are profoundly dependent on the Pediatric Brain Tumor Foundation’s seed funding to prove their research’s efficacy and secure the large-scale government funding that can further their scientific breakthroughs. Every dollar the Pediatric Brain Tumor Foundation invests in research attracts an additional 12 dollars in follow-on funding for new scientific exploration.

To help us continue providing this important research funding, you can participate in our year-end holiday giving campaign, which aims to raise $365,000 by January 1st. Your donation is tax-deductible and supports our efforts to fund and advocate for scientific discoveries and provide pediatric brain cancer patients, survivors, and their families with the resources they need. To learn more or make a donation, visit curethekids.org/holiday2022. The results of Dr. Reitman’s research can be found here.

 

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