Targeted Therapies for High-Risk Pediatric Brain Tumor Subtypes

Brain cancers are the most common solid tumors in children, accounting for 20 percent of all childhood cancers. Many of these cancers are high-risk, meaning that they are prone to relapse and have a low 5-year survival rate. Each type of brain tumor also includes subtypes with radically different origins, biology and prognoses. Current treatments – a combination of surgery, radiation and conventional chemotherapy, are not effective at curing these cancers.

Dr. Gilbertson at Cambridge University received a CureSearch Acceleration Initiative Award to discover and develop new therapies for three high-risk pediatric brain cancers: medulloblastoma, ependymoma and choroid plexus carcinoma. Dr. Gilbertson’s team tested new and existing drugs for these specific diseases and identified several promising therapies to guide immediate clinical testing. Results of this project contributed to the launch of a phase 1 clinical trial testing combination therapies for malignant brain tumors with Dr. Gilbertson’s research directly impacting patients with recurrent, refractory medulloblastoma. The trial, sponsored by St. Jude Children’s Research Hospital, opened March 5, 2019.

Notably, thanks in part to the strength of the work supported by CureSearch, Dr. Gilbertson’s institution was designated as the first Cancer Research UK Children’s Brain Tumour Centre of Excellence.

As of the conclusion of his CureSearch-funded project, Dr. Gilbertson has carried new therapies for high-risk brain cancer closer to and into clinical trials:

• 1 drug in preclinical testing for treatment of choroid plexus carcinoma
• 3 drugs in preclinical combination therapy testing for high-risk medulloblastoma
• 1 Phase I clinical trial initiated for high-risk medulloblastoma based on data obtained during the award period
• 1 novel craniospinal irradiation protocol developed for testing combination of drugs with radiotherapy in medulloblastoma models
• 15 orthotopic human xenografts of pediatric brain cancer established
• 1 first-of-its-kind spontaneous mouse model of ependymoma developed
• 1 novel genetically engineered mouse model of choroid plexus carcinoma and 1 high-risk medulloblastoma mouse model created
• 2 million drugs screened in ependymoma
• 92 compounds assessed in a combination drug screen developed to determine therapies for high-risk medulloblastoma