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St. Jude Children's Research Hospital Home
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Explore our cutting edge research, world-class patient care, career opportunities and more.
St. Jude Children's Research Hospital Home
Improving the prognoses of children with brain tumors through the creation of improved therapies guided by a comprehensive understanding of disease pathogenesis and normal brain development
Brain tumors are the leading cause of cancer-related deaths in children. Despite recent advances in understanding disease biology, treatment approaches are still lacking for some patients and lead to long-term, debilitating side effects in others. The goal of the Neurobiology and Brain Tumor Program (NBTP) is to improve survival and morbidity of children with brain tumors by developing the most effective, least toxic therapies through a better understanding of disease pathogenesis and normal brain development.
NBTP research focuses on four aims:
Department of Developmental Neurobiology
Members of the NBTP are focused on understanding the underlying pathogenic processes that drive brain tumor development. Their work has already revealed novel insights into the mechanisms of oncogenic activity of pediatric high-grade glioma (HGG) and medulloblastoma (MB) and facets of how the immune system interacts with brain tumors.
They identified an oncohistone mutation that affects growth of the deadliest HGG, called high-grade diffuse midline glioma (DMG); furthermore, this mutation shows potential as a therapeutic target. By using patient-derived HGG models, researchers also discovered a clinically relevant compound that disrupted the DNA damage repair mechanism and increased the efficacy of radiation with little toxicity. This is being developed into an upcoming clinical trial.
Single-cell sequencing was used to probe the heterogeneity within and between MB tumors, and the findings helped researchers understand the cellular and developmental states underlying subtype-specific MB biology. Work performed by the NBTP also discovered that G3 and G4 MB—thought to be distinct disease entities—actually comprise a clinical spectrum with biological and clinical overlap. This finding, in conjunction with the discovery of a common predisposition gene for MB, has clinical significance and will shape the way that children with MB are treated.
The NBTP has advanced CAR T-cell therapy in a variety of ways such as: identified a promising antigen for relapsed or refractory brain tumors such as MB and DMB; enhanced antitumor activity and proliferative capacity of CAR T cells; discovered new molecular targets
The NBTP brings together expertise in fundamental neurobiology, cancer biology, translational research and clinical research to focus its integrated efforts. Members of the NBTP share a common vision that emphasizes the integration of laboratory and clinical research to advance cures for pediatric brain tumors.
Understanding the relationship between disease and prognosis is an area of active research in the NBTP. The ability to molecularly stratify patients (and disease) based on genetic characteristics and use this information to inform treatment strategies and predict prognoses is transformative. NBTP members have used a variety of state-of-the-art molecular stratification approaches to more comprehensively understand several pediatric brain tumors such as:
The data collected from NBTP-led studies is used to establish new clinical trials that advance therapy, improve survival and lower morbidity in children with CNS tumors. In addition to clinical trials pertaining to the above-mentioned studies, program members are clinically investigating:
As survival improves, the NBTP focuses on decreasing morbidity and improving quality of life by better understanding the cause of toxicity-related injury and deploying innovative interventions to mitigate these risks. Studies from NBTP investigators found that young children with brain tumors experience cognitive difficulties affecting quality of life. The study provides new insights for better treatment planning, especially since changes in cognitive function depended on tumor location and surgical factors rather than adjuvant therapy.
Researchers also showed that cognitive outcomes were improved in patients with craniopharyngioma receiving proton therapy as opposed to a historical cohort. These findings represent a new benchmark to which other regimens can be compared and sets a new practice-changing standard.
A subset of children who undergo surgical extraction of brain tumors in the posterior fossa will experience posterior fossa syndrome (PFS). PFS significantly impacts speech and affects quality of life. Members of the NBTP identified regions of connectivity in the midbrain that, when damaged, cause PFS. These findings inform surgical planning and even suggest strategies for cognitive rehabilitation.