EXAMINING PROLIFERATION AND INVASION OF DRUG TREATED GLIOBLASTOMA AND GLIOBLASTOMA STEM CELLS IN EX VIVO SLICE CULTURES
Date
2024-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Glioblastoma (GBM) is classified as a Grade IV astrocytoma by the World Health
Organization, the most severe classification for tumors in the central nervous system on
account of its aggressive invasion. Because of GBMs’ aggressive growth, glioblastoma is
associated with a poor prognosis and has a median survival time of between 14 and 15
months postdiagnosis. Glioblastoma is highly resistant to treatments and resistance is
hypothesized to be connected to Glioblastoma Stem Cells (GSCs), which have proven
resistant to anti-cancer treatment and have an outsized effect on tumor formation. A major
molecule known to increase GBM motility and invasion is the L1 Cell Adhesion Molecule
(L1CAM). As traditional therapies have poor treatment outcomes and significant side
effects, newer, targeted therapies have been proposed. The first entails using small
molecule inhibitors, capable of binding to intra- and extracellular targets and crossing the
blood brain barrier to disrupt cellular processes of cancer cells involved in motility and
proliferation. The second proposed new therapy is blocking antibodies, which have shown
the ability to disrupt cell migration in other cancers. My goal is to test the effectiveness of
these two new treatment candidates on the ex vivo brain slice model, which combines the
positives of in vivo and in vitro models into one model.
I provide evidence that small molecule inhibitors reduce the extent of invasion of
GBM cells both expressing and lacking L1CAM in the ex vivo brain slice model. I discovered
that undifferentiated GSCs also had reduced extent of invasion following the small molecule
inhibitor treatment. I was unable to prompt a differentiation of GSCs, which would create a
more representative tumor model. Additionally, the blocking antibodies failed to produce
significant reductions in invasion extent.
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These findings suggest that the small molecule inhibitors tested are a candidate for
further clinical research, potentially in mammal models. The ex vivo brain slice model was
found to be efficient and capable system of quantifying the extent of glioblastoma into chick
embryo brain slices. Further research should also entail testing other blocking antibodies
in the ex vivo brain slice model to determine efficacy of the treatment possibility.