ATM Inhibition as a Radiosensitizer in DIPG Pre-Clinical Trials

  • Becher, Oren Josh (PD/PI)

Project: Research project

Project Details


Diffuse Intrinsic Pontine Glioma (DIPG) tumors account for 10-15% of all brain tumors in children. Unlike many other pediatric cancers, there has been little progress in improving treatments and survival rates for DIPG over the last few decades. These aggressive tumors typically result in death within two years of diagnosis. The current standard-of-care is conventional radiation therapy (RT), although this provides only temporary relief from symptoms and does not represent a cure. Moreover, while numerous clinical trials of new therapies have been performed, no chemotherapeutic agent has demonstrated significant efficacy. This lack of efficacy is likely the result of early studies using adult glioma as a pre-clinical model. Research has revealed that DIPG is biologically distinct from adult glioma. Therefore, pre-clinical trials using DIPG-specific models to test novel therapies are needed to improve outcomes for children. We have developed a genetically engineered mouse model of DIPG that faithfully replicates the human disease in children and represents a novel platform with which to study the biology and treatment of DIPG. Using this model, we propose to conduct a pre-clinical study of the drug AZ59 to examine its ability to improve the efficacy of RT. We hypothesize that AZ59 will inhibit the protein ATM (Ataxia telangiectasia mutated), which plays a central role in cell division and DNA repair, and, by doing so, will sensitize this DIPG model to RT. We expect this to result in slowed tumor growth and a prolonged lifespan for treated animals with brainstem tumors.
Effective start/end date12/31/178/31/19


  • Ann & Robert H. Lurie Children’s Hospital of Chicago (925675-NU // 925675-NU)
  • Hyundai Hope On Wheels (925675-NU // 925675-NU)


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