Diffuse Intrinsic Pontine Glioma (DIPG)

Development of novel pediatric brain tumor radiosensitizer

Pediatric brain tumors are devastating cancers and often are very aggressive, despite surgical resection, high-dose radiotherapy and chemotherapy. Shown in the first slide below is a 12-month-old female with an atypical teratoid/rhabdoid tumor (ATRT) who we treated recently at Yale, shortly before she succumbed to her disease. They often recur at the original site of disease, suggesting a need for better local control. Our laboratory is screening for novel radiosensitizers that target the INI1 mutation in ATRT cells.

Similar to ATRT, diffuse intrinsic pontine glioma (DIPG) is an aggressive primary tumor affecting the pons region of the brainstem in children. It is nearly 100% fatal in children afflicted with the disease, and again it is a local control problem. Radiation therapy is the only measure that can prolong survival, since these tumors are unresectable. We have acquired primary DIPG specimens from our collaborators, and we have developed in-house methods to growth them in 96- and 384-well microplates, and to image them growing as live spheroid cultures. We will screen these cultures for novel radiosensitizers.

Finally, pediatric high grade gliomas (HGGs) are tumors where local control yet again is a major barrier to treatment efficacy. We now know these are genetically distinct tumors from adult HGGs, and yet children continue to receive “adult HGG” experimental therapeutics. We have collected a large cell line panel of established and primary pediatric HGG cell lines, and we are attempting to model pediatric-specific HGG mutations in these tumors. We are actively screening for novel radiosensitizers.