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Tumor Discovery Understanding glioblastoma invasion and therapy

There is currently no standard-of-care treatment of monomeric protein building blocks that organize into
protocol for recurrent GBM. Repeat surgical resection is higher-order filamentous polymers. The fundamental
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sometimes appropriate, though patient quality of life must protein unit of microtubules is tubulin. Microtubules
be considered alongside the potential survival benefits also cycle through phases of gradual polymerization and
provided by a second operation. Patients commonly rapid depolymerization at the plus end. A large cohort
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pursue treatment with bevacizumab – an anti-vascular of microtubule-binding proteins regulates microtubule
endothelial growth factor monoclonal antibody – but dynamics through a diverse set of functions, such as
it has not been shown to increase overall survival and nucleation, capping, trafficking, stabilizing, destabilizing,
may instead increase invasive infiltration of the brain. 49,50 bundling, cross-linking, and integration with other
Other commonly pursued treatment options at the time of cytoskeletal elements. 63
recurrence include carmustine and experimental therapies Microtubules participate in a wide variety of cellular
through clinical trial enrollment. processes. They form portions of the mitotic spindle
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5.4. Cause of death apparatus that separate sister chromosomes. They are
scaffolds for motor-driven cellular trafficking, and their
The end-of-life phase of GBM is characterized by a ultrastructural organization within the cell plays a large
significant progression of neurological deficits. The role in determining the distribution of other intracellular
majority of GBM patients exhibit decreased consciousness, organelles. This makes microtubule organization
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dysphagia, and fever within the last days of life. 51,52 Seizures, extremely important for cells that require polarity to
headaches, and incontinence are also common. 53,54 execute physiologic functions (i.e., neurons and brush
Terminal-phase GBM patients report significantly lower border epithelia), as a loss of microtubule organization
rates of bodily pain than other cancer patients, but much leads to a profound disruption in internal cellular
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higher rates of depression and cognitive dysfunction. organization. Microtubules are important mediators of
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56
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Causes of death routinely reported in GBM patients cellular motility, and this is especially true in neurons and
are associated with increased ICP and diffuse tumor astrocytes where lamellipodial extension is limited, and
infiltration of the brain and brainstem and include brain microtubules closely underlie the leading edge membranes
herniation, seizure, tumor-related brain hemorrhage, and of migrating cells and developing neuritis. 66
dyspnea or respiratory arrest. 57,58
The most genetically diverse class of cytoskeletal
6. Roles of the cytoskeleton in GBM fibers is the intermediate filaments, which are a family of
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The cytoskeleton is an organized and dynamic meshwork cytoskeletal fibers derived from 73 different genes. Despite
of protein filaments that reinforce cell membranes, provide substantial genetic diversity, intermediate filaments are
cells with shape/structural integrity, and facilitate essential remarkably consistent in size. 68,69 Intermediate filaments
cellular functions. In eukaryotic cells, the cytoskeleton exhibit a high degree of homology in their sequences and
is composed of three classes of filamentous fibers: actin, structures. 70
intermediate filaments, and microtubules. Intermediate filament expression profile varies greatly
Actin is a ubiquitous and evolutionarily conserved by cell and tissue type. For example, keratins are highly
protein that makes up approximately 15% of the total protein expressed in epithelial cells, whereas mesenchymal cells
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in human cells. The actin cytoskeletal system is composed more commonly express vimentin. The intermediate
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of monomeric or globular actin (G-actin) and filamentous filaments GFAP and Nestin are particularly relevant to
actin (F-actin). F-actin forms through the polymerization GBM biology. GFAP is used as a glial cell marker in GBM
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of G-actin monomers into a polarized, double-stranded diagnostics, and Nestin is a well-established marker of
helical fiber. Actin filaments are highly concentrated at CNS neural progenitor cells that are also detected in GBM
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the cell periphery and form organized arrays of bundles stem-like cells (GBMSC). 71
and networks that underlie and give structure to the plasma 7. GBM invasion and the cytoskeleton
membrane. Manipulation of the balance between F-actin
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polymerization/depolymerization underlies the generation 7.1. Invasion patterns in GBM
of different types of membrane-deforming forces required Macroscopically, GBM favors invasion along pre-existing
for cellular motility and many other essential homeostatic CNS structures, such as the white matter tracts (i.e.,
processes, such as endocytosis and cytokinesis. corpus callosum) and blood vessels (i.e., perivascular
Microtubules are long polarized fibers. Like all space/Virchow Robin Space). Migration within the
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cytoskeletal filaments, microtubules are composed of arrays subarachnoid/leptomeningeal space, which is continuous
Volume 4 Issue 2 (2025) 26 doi: 10.36922/td.8578