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Development of Targeted DNA-damaging Therapy for ATRX-deficient Pediatric Glioblastoma

University of Michigan
Carl Koschmann, MD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Brain Tumors, Glioma
Project Description: 


Brain tumors are the leading cause of death among childhood cancers.  Despite recent data showing differences in mutated genes in childhood and adult glioblastoma, the treatment is the same for both patient populations. The ATRX gene is mutated primarily in adolescent patients with glioblastoma, a devastating and highly malignant brain tumor.  Treatments for human cancer are becoming increasingly personalized, and ATRX loss allows for a promising target for individualized treatment for patients with glioblastoma.

Project Goal

We have recently developed the first model of mouse glioblastoma with the loss of the ATRX gene. This model will allow us to further study the impact of ATRX mutation and develop targeted therapies for this patient population. Temozolomide is the standard of care for adult and pediatric glioblastoma, but recent studies have questioned its efficacy in pediatric patients. Indeed, treatments of our glioblastoma tumor cells, with and without ATRX loss, show little cytotoxicity with various doses of temozolomide. However, treatment of tumor cells generated from our mouse models has shown that loss of ATRX creates a susceptibility to other agents that are not frequently used in pediatric patients with glioblastoma. We intend to further these studies by growing tumor cells from human pediatric patients with ATRX loss and confirming promising DNA-damaging agents and radiation regimens. As well, we will see if ATRX loss causes sensitivity to a DNA-damaging genetic therapy.  Based on our lab's previous translational successes, we are optimistic that our work will result in improved therapy for adolescent patients with glioblastoma.


"I am thrilled to have been selected as a recipient of the Alex’s Lemonade Stand Young Investigator Grant for our project.  The funding will be pivotal in my ability to continue research with the goal of improving treatments for pediatric patients with brain tumors.  The financial support will help me solidify my plans to pursue a career as a physician scientist in Pediatric Neuro-Oncology.  Personally, it is very rewarding to have the support and affiliation of Alex’s Lemonade Stand, an organization which is so important for pediatric cancer research." ~ Carl Koschmann, MD

Co-funded by: 
Northwestern Mutual Foundation