Circulating Exosomes as Biomarkers of Medulloblastoma Progression, Metastasis, and Recurrence
Medulloblastoma is the most common malignant pediatric brain tumor and, unfortunately, nearly one-third of affected children ultimately die of the disease despite aggressive therapy. High-risk medulloblastoma and recurrent tumors portend an even poorer prognosis. To improve patient outcomes, our primary goal is to improve methods to noninvasively detect tumor progression or relapse at early stages that will likely offer therapeutic opportunities or alter treatment strategies.
Specifically, we seek to determine whether secreted tumor vesicles, called exosomes, isolated from the plasma of medulloblastoma patients can serve as a surrogate for tumor tissue to identify therapeutic targets as well as monitor disease status following treatment. We propose studies that incorporate tumor-specific exosomal isolation and protein profiling using a novel genetically relevant mouse model of medulloblastoma. We will use this animal model to identify tumor-specific exosomal protein profiles from plasma during medulloblastoma progression and at tumor recurrence following standard radiation therapy. We will correlate these results with analogous analyses of circulating exosomal profiles of human medulloblastoma including at initial diagnosis and following standard therapy.
We predict our studies will aid in noninvasively identifying disease progression including recurrent disease at earlier time points in medulloblastoma patients resulting in earlier treatment initiation, higher treatment intensity, or potential use of novel experimental therapies in order to improve outcomes. Furthermore, we predict this work will provide proof-of-principle for our approach for translational biomarker analysis of other neural and non-neural pediatric cancers.
"This research support provided by ALSF through the Innovation Award will allow us to develop and validate new blood test-based biomarkers for medulloblastoma, the most common malignant brain tumor of childhood. These biomarkers may allow us to monitor response to standard and novel therapies in patients as well as potentially detect tumor recurrence at earlier stages in order to guide therapeutic decisions.” - Parveen Raju