What Is the Main Idea?

Glioma is a type of tumor that develops in the nervous system, with differences between gliomas that develop in children and adults. In the open-access review article “Pediatric Glioma Models Provide Insights into Tumor Development and Future Therapeutic Strategies”, published in the journal Developmental Neuroscience, the authors summarize different experimental models that are being used to study glioma in children and how they may contribute to improvements in its treatment.

What Else Can You Learn?

Glioma and its symptoms are described. Differences in gliomas arising in children and adults, driver mutations, and the use of experimental models in cancer research are also discussed.

What Is Glioma?

Glioma is a type of tumor that is found in the nervous system. It usually develops in the brain but can also develop in the spinal cord (a tube of nervous tissue that runs from the brain to the lower back), although this is rare. Glioma develops when glial cells begin to develop and grow out of control. There are different types of glial cell and they play essential roles in the nervous system that support the function of neurons (cells that transmit messages from one part of the nervous system to another via electrical impulses), with glial cells sometimes being described as the “glue” that holds the nervous system together.

As well as surrounding neurons and holding them in place, glial cells also create a myelin sheath around neurons that insulates their electrical impulses so that they can transmit messages effectively, a bit like the coating of an electrical wire. They supply oxygen and nutrients to neurons to keep them nourished, regulate inflammation (an immune system process through which the body responds to an injury or a perceived threat, like a bacterial infection or damaged cells). They also form the blood–brain barrier, which is a barrier between the blood vessels in the brain and the other components that make up brain tissue that allows nutrients to reach the brain while preventing other things from entering it that could cause infections or damage.

What Are the Symptoms of Glioma?

There are different types of glioma, depending on the type of glial cell from which the glioma develops and speed at which the tumor is growing. As a result, the symptoms and signs of glioma can vary between people, and are also affected by where the tumor is in the nervous system and its size. Common symptoms are:

  • headache, which may hurt more in the morning;
  • changes in mental function (such as problems with understanding information and memory) and personality;
  • feeling sick and vomiting;
  • problems with vision (such as blurred or double vision);
  • seizures, especially if the person has not had them before.

Gliomas can develop at any age, and although glioma is most commonly diagnosed in adults there are some types of glioma that are more common in children and young adults.

What Did This Article Look at?

Review articles survey the information that has been published on a topic to date. Rather than presenting new findings from their own research, the authors aim to clarify current thinking on a topic and the evidence that supports it, and sometimes set out suggestions for changes to what is considered to be best practice.

In this article, the authors review the different experimental models that are being used to study glioma in children and summarize how these models may contribute to improvements in its treatment. Experimental models use systems, such as the culturing of cells in a laboratory, to investigate processes that are thought to be involved in diseases and to evaluate new drugs that are being developed before they are assessed by going through the clinical trials process in humans.

There is a need for new treatments for glioma in children. Treatments that are currently the standard of care for childhood glioma have been chosen based on their effects on gliomas in adults, but adult and child gliomas that are high-grade (this means that they are “malignant”, growing in an uncontrolled way and able to spread to nearby tissues and other parts of the body) progress differently and have different underlying “driver mutations” (these are changes in genes in the tumor cells that give them a growth advantage and, as a result, promote the development of cancer).

Until recently, a lack of experimental models that could accurately recreate the environment in which gliomas form meant that efforts to study child gliomas were limited. However, the discovery of child glioma-specific driver mutations has enabled researchers to investigate the origins of these tumors, laying the foundation for the development of more appropriate and effective treatments.

What Experimental Models Are Being Used?

Over the last 10 years there have been major advances in the development of cell lines (a population of cells that can be grown and maintained in a laboratory) and models derived from tissue samples obtained from glioma patients during surgical procedures. Cell lines have the advantages of being relatively cost-effective and easily shared with other researchers, as well as being suitable for use in high-throughput screening (this is a process by which hundreds of samples of cells and hundreds of different potential drugs can be tested quickly, often using robotics).

Advances in stem cell engineering have also opened up new opportunities to investigate the development of glioma. Stem cells are unique in that they can self-renew, are either undifferentiated or only partially differentiated, and are the source of specialized cell types, like red blood cells and types of brain cell. Stem cells are useful in glioma research because they can be used to model tumor types from which it is difficult to obtain tissue samples or establish cell lines, which is the case for some types of glioma, and they can be controlled so that specific cell types and driver mutations can be investigated.

Organoids are three-dimensional tissue cultures that are grown from stem cells. Although cell cultures can be very useful in cancer research, they are usually grown as flat sheets of cells in tissue culture flasks and do not accurately represent all of the complicated interactions that take place between tumor cells and their environment in the body. This “tumor microenvironment” includes immune cells, signaling molecules, the matrix that surrounds cells in tissues and supports them, and the surrounding blood vessels. Tumors and their surrounding microenvironment constantly interact and it is known that they can influence each other.

Immune cells in the microenvironment can affect the growth and development of tumor cells, while a tumor can influence its microenvironment by releasing signaling molecules that promote the development of new blood vessels, which increase the supply of nutrients to the tumor and aids its ability to start to spread around the body, and inhibiting and evading the immune system’s ability to recognize and destroy tumor cells. Using organoids enables elements of the tumor microenvironment to be incorporated into models of glioma so that the experiments more accurately mimic the situation in the body.

These model systems are enabling us to better understand how glioma develops. As our understanding increases, more features of glioma cells will be identified that can be targeted specifically by new treatments, increasing the range of therapies that can be used to treat glioma in children and improving the outcomes of patients.

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