(Image by Getty Images)

A splitting headache that continues non-stop. A weakness in the muscles and being unable to walk a small distance. Feeling abnormally sleepy at random periods of the day.

For many individuals with glioblastoma (a type of brain tumor), these symptoms were generally dismissed as the body feeling generally unwell. Even when non-cancer patients think of these symptoms, a condition as deadly as glioma would not be the first thing to come to mind. Unfortunately, these subtle symptoms can transform into a rapidly-progressing disease with minimal chance of survival.

52% of all primary brain tumors are glioblastoma, and 17% of all tumors in the brain are a glioblastoma (whether the tumor is primary or metastatic doesn’t matter). Despite the tumor more commonly occurring in individuals between ages 45–70, the median survival rate for brain cancers is around 1–2 years, which is devastating. GBM is evidently becoming a larger problem, and research is imperative to reduce the progression of this disease.

As scary as this sounds, recent breakthroughs are beginning to change the way we look at glioblastoma. Interested to learn more? Let’s take a look at this seemingly deadly cancer and recent studies about it.

A Brief Introduction to the Brain

To understand the nature of glioblastoma, we require a general understanding of the different regions in the brain. Despite the brain being known for being overly complex, the two most important sections to note are the cerebrum and the cerebellum.

A general diagram of the brain (Image by Colorbox).

The cerebrum refers to the anterior part of the brain that’s located towards the front of the skull, and is much larger compared to the cerebellum. The cerebrum can be divided into many subsections with varied function, but the purpose of the cerebrum includes recognizing external surroundings, problem-solving, and coordinating movement.

With regards to a brain tumor, most cases (regardless of whether it’s benign or malignant) will occur in the cerebrum. Tumors in the cerebrum are also referred to as supratentorial since they are present above the tentorium, which is a fissure that divides the cerebrum from the cerebellum. The cerebrum also contains ventricles with cerebrospinal fluid, which is responsible for protecting the brain while providing bouyancy.

The sections of the cerebrum (Image by Depositphotos).

While the cerebrum is above the tentorial line, the cerebellum is below this fissure and also neighbors the brain stem. While the cerebrum is split into several sections, the cerebellum has two important subsets to note: the cerebellar cortex and cerebellar nuclei.

The cerebellar cortex consists of three layers:

  • The outermost layer is made of the axons and dendrites of cerebellar neurons, indicating it contains a majority of the cerebellum’s neurons.
  • The middle layer contains Purkinje cells, which are a type of flask-shaped neuron native to the cerebellum. The primary function of these cells is the emission of GABA (gamma-aminobutyric acid), a neurotransmitter that regulates nerve impulses throughout the brain and controls motor function.
  • The innermost layer has granular cells, which are the smallest type of neuron in the brain. These cells send impulses to the Purkinje cells in the cerebellum, which move into the outermost molecular layer throughout the cerebellar cortex. These granule-cell — Purkinje-cell synapses are super important for the brain, and they use glutamate as a neurotransmitter.

On the other hand, the cerebellar nuclei is the innermost section of white matter of the cerebellum. This subsection will receive inhibitory signals from Purkinje cells (usually from the cerebellar cortex) and is responsible for communicating such signals throughout the brain. Within this inner white matter, the four types of deep cerebellar nuclei are:

  • Dentate
  • Emboliform
  • Globase
  • Fastigii

Tumors are rarely found in the cerebellum, but these infratentorial tumors (since the cerebellum is below the tentorium) can also be located in the brain stem and other neighboring structures.

A more complex diagram of the brain (Image by diagramchartspedia.com).

Where and How Glioblastoma Starts

Now that we have a general understanding of the brain’s anatomy, let’s look at the nature of a glioblastoma. More often than not, GBMs are supratentorial tumors and are also a type of astrocytoma, which is a brain tumor originating from astrocyte cells in the brain.

In the central nervous system (CNS), astrocytes are a type of glial cell that perform a number of functions throughout the brain and spinal cord. Some of their key purposes are supporting synapses (which relay electrical signals between neurons), controlling the blood-brain barrier, and regulating blood flow throughout the brain. Depending on the type of astrocyte, they will either be located throughout the CNS or primarily in white matter, a characteristic of more fibrous glia.

An image of an astrocyte (Image by iStock).

Though astrocytes are the primary cause of glioblastoma, the reason behind their sudden abnormality remains a mystery. Scientists have discovered that a number of mutations within astrocytes have likely caused the development of cancerous cells in the brain, but the cause of these mutations isn’t well-known either.

In 2018, researchers discovered that a mutation in the most commonly-used protein in astrocytes led to consequences that were shockingly similar to that of a brain tumor. The protein, GFAP (glial fibrillary acidic protein), is a type of cytoskeleton protein that allows for astrocytes to remain in a star-shaped structure. The leader of this study and a neuroscience professor at the University of Wisconsin-Madison, Su-Chun Zhang, led this study and began her research by growing adult astrocytes from patients with extensive neurodegeneration and converting them into stem cells.

When observed more closely, the astrocytes contained excessive tangles of the GFAP protein and seemed to be taking a toll on these cells’ functionality. When the converted stem cells experienced gene editing to correct the incorrectly folded GFAP protein, the cells were good as new! This discovery is astronomical for determining the causes of neurodegeneration brought on by cancerous cells, and gives us significant insight on potentially stopping this rapidly-progressing malignancy.

An image of GFAP highlighted in astrocytes (Image by Aves Labs).

Recent Breakthroughs in Glioblastoma Research

In a world of rapidly-progressing technology, there have been several breakthroughs in glioblastoma research and working towards stopping it altogether. Here are some instances of notable research conducted by scientists on brain tumors:

In July 2020, a recent study was published on improving the current radiation therapy used for glioblastoma. Instead of directly targeting the tumor (which is the norm for most radiation therapy), the researchers in this study wanted to target a specific metabolic pathway that worked towards repairing damaged DNA. The senior study author, Daniel Wahl, M.D., PhD., explains that preventing the repair of DNA after radiation therapy will inhibit the cancerous cells from returning since the genetic information to generate these cancerous cells will be entirely destroyed by attacking a specific metabolic pathway.

A cartoon depiction of radiation therapy (Image by Tera Vector).

In March 2019, research revealed that instead of targeting the glioblastoma cells in a brain tumor, drug options should be attacking stem cells that divide relatively slowly to eliminate further progression of the cancer. Researchers believed that while radiation therapy and chemotherapy are effective at stopping the rapidly-multiplying cancerous astrocytes, the glioblastoma stem cells are the real culprits that are constantly allowing this malignant brain tumor to return immediately. The study eventually concluded that the use of a synthetic drug Gboxin was the most effective at reducing the accumulation of tumors in the brains of mice.

Several images of glioblastoma stem cells (Image by Spandidos Publications).

In June 2019, a team of researchers found a number of previously undiscovered biomarkers in glioblastoma using the Cancer Genome Atlas. The discovered biomarkers are revolutionary to personalizing treatment options for patients since they determine which types of patients will heal fastest from chemotherapy or radiation therapy. To look for these biomarkers, research was started by generating patient-derived tumors in mice and providing different treatment options to these animals. Based on the results and general health of these mice, the scientists looked at gene transcripts to determine which genes were allowing mice to experience positive effects associated with their treatment.

A sample image of a gene transcript (Image by Biostars).

Key Takeaways

  • Glioblastoma is a malignant brain tumor and is considered one of the deadliest brain cancers. This condition originates from mutated astrocytes found throughout the central nervous system, which begin growing at an uncontrollable rate.
  • In the brain, the two critical sections to note are the cerebrum and cerebellum. While tumors in the cerebrum are called supratentorial, tumors in the cerebellum are referred to as inratentorial.
  • Glioblastoma is allegedly caused by the misfolding of the GFAP protein in astrocytes, which is responsible for their structure. A single mutation in this protein causes astrocytes to exhibit behavior similar to that of cancerous cells.
  • There is a lot of notable research in finding treatment for glioblastoma, most of which concerns changing current treatment methods.

I’m a 15-year old interested in neuroscience, genomics, and entrepreneurship | LinkedIn: https://www.linkedin.com/in/sahasra-pokkunuri-345a711b7/

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