Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor and despite ∼70% five-year survival with current therapies, nearly one-third of children relapse. MB recurrence results in an extremely poor prognosis with a three-year survival rate of 18%. Although routine MRI surveillance enables detection of asymptomatic recurrences, patient outcomes have not been significantly improved. Moreover, early detection of microscopic disease by contrast-enhanced MRI scans present detection problems including signal heterogeneity and low contrast uptake as well as sedation risks in young children. We seek to address the challenge of early MB recurrence detection by utilizing a nanotechnology tool capable of sensitive, selective and rapid response to local biomarkers in vivo and detection of tumor biomarkers ex vivo from patient liquid biopsies. Using a physiologically relevant GEM model of SHH subtype MB (Ptf1acre/+;Ptch1fl/fl), we found that exosomal miR-17∼92 cluster components represent the top 1% of miRNAs secreted from advanced stage SHH MB explants. We similarly detect exosomal miR∼17-92a components from plasma of human SHH MB patients compared to healthy controls. Analysis of plasma from late-stage SHH MB mice revealed that only miR-19 expression levels significantly correlated with tumor progression from early hyperplasia to late-stage MB including a reduction in plasma exosomal miR-19 levels following radiation treatment. These data support utility of miR-19 as a biomarker of primary MB tumor progression and treatment response, and potential detection of tumor recurrence. We are now utilizing a novel nanotechnology tool that allows for noninvasive longitudinal detection of miR-19 (or other potential microRNA biomarkers) through miRNA hybridization events using an optical nanosensor (single walled carbon nanotubes, or SWCNTs). We are developing methods to encapsulate this SWCNT miR-19 nanosensor in a hydrogel and implantation into the resection cavity of SHH MB GEM mice to noninvasively detect increase in miR-19 hybridization events in vivo as a readout of local SHH MB tumor recurrence.
Mustafov et al. (Fri,) studied this question.
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