Identifying Brainstem Glioma Subtypes That Can Be Radiosensitized by ATM Inhibition

Radiation treatment temporarily ameliorates some neurological symptoms caused by diffuse intrinsic pontine glioma (DIPG). However, the tumor invariably recurs. Inhibitors of ATM, a serine/threonine kinase, interfere with DNA damage-sensing and are currently in clinical trials for adults with gliomas and brain metastases. ATM inhibition is known to selectively radiosensitize tumors that have inactivated p53 function. Dr. Reitman found that brainstem gliomas frequently contain mutations in key components of the p53 pathway and therefore hypothesizes that brainstem gliomas will be susceptible to radiosensitization by ATM inhibition. Positive results will provide the pre-clinical foundation for clinical trials in children with brainstem gliomas and define genetic biomarkers of response to treatment.