The Role of Glioblastoma Foundations in Research and Treatment

Monday, July 24, 2023


Glioblastoma is the most common and deadly form of brain tumor in adults. Presently, it is incurable. We must understand why and how this tumor forms and develop newer, more effective therapies.

Immune responses to Glioblastoma may be impaired by several mechanisms, including the BBB, lack of lymphatic channels, low basal expression of Major Histocompatibility Complex (MHC) class II molecules, and immunosuppressive cytokines.

Development of Drug Therapies for Glioblastoma

Unfortunately, there is no cure for Glioblastoma multiforme (GBM). But treatment can help manage symptoms and prolong life. The first step is surgery, which aims to remove as much of the tumor as possible. If the surgeon can't remove it, radiation therapy kills the remaining cancer cells and prevents new ones from growing. It is often given with chemotherapy, mainly the oral drug temozolomide (Temodar).

Other therapies might be helpful for some patients. These include antiseizure drugs, which can reduce the risk of seizures, and corticosteroids, which can decrease brain swelling and ease headaches.

Getting a full workup by a team of Glioblastoma Foundation professionals—including neurologists and neuro-oncologists- is important for a patient. They may recommend a clinical trial that could improve your odds of survival. 

Targeted Therapies for Glioblastoma

The five-year survival rate for Glioblastoma Multiforme (GBM) patients is below 10%. The primary treatments for brain tumors are surgery, chemotherapy and radiation therapy.

Researchers are focusing on developing targeted therapies that can improve patient outcomes. These drugs can target specific dysregulated pathways in a cancer cell and block the growth of new tumor cells.

These targets include receptor tyrosine kinases, phosphatidylinositol 3-kinase/AKT/mTOR pathway, DNA damage response and TP53. Small molecule inhibitors of these specific pathways are showing promising results in Glioblastoma.

One example is vorasidenib, which targets IDH mutations in Glioblastoma. It prevents the formation of an onco-metabolite called 2-Hydroxyglutarate, produced by mutant IDH1/2. Vorasidenib can double the time patients with IDH-mutated Glioblastoma go without their tumors worsening, which can delay the start of radiation and chemotherapy.

Another example is bevacizumab, which is given with lomustine and inhibits a protein that helps tumor cells grow. It can treat Glioblastoma and other brain and spinal cord tumors, including subependymal giant cell astrocytomas that surgery can't completely remove.

Immunotherapy for Glioblastoma

Glioblastoma multiforme (GBM) is a high-grade brain tumor that arises from the brain's glial cells. These cells normally support and nourish neurons and form scar tissue that helps the brain heal after injury. GBMs are aggressive and can spread to healthy brain tissue. They are also often associated with genetic diseases such as neurofibromatosis type 1 and Li-Fraumeni syndrome.

Immunotherapy, a cancer treatment that boosts the patient's natural immune system response, has shown promising results in other cancers and may help improve survival for glioblastoma patients. This therapy involves giving the patient antibodies that target specific tumor cells and vaccines to amplify the body's natural response.

Many glioblastomas recur, and new treatments are needed to extend survival. Researchers are testing a variety of experimental therapies, including immunotherapy. They study combinations of medicines and other strategies, such as gene therapy, to deliver anti-cancer genes to tumor cells. Patients interested in participating in clinical trials should speak with their doctor to learn more about available options.

Clinical Trials for Glioblastoma

Currently, most glioblastoma patients are treated with standard therapy, which only postpones tumor recurrence. With no cure in sight, the need for new treatments is urgent.

Glioblastoma Foundation-funded research is making a difference, but much more needs to be done. We are committed to breaking down barriers that prevent effective treatments from reaching the patients who need them.

One of these barriers is overly restrictive eligibility criteria, which reduces the number of patients who can participate in clinical trials. Another is the difficulty of turning promising Phase II results into a randomized Phase III trial.

One exciting new opportunity is to utilize a patient's immune system to fight cancer, and a Penn Medicine team is leading the way in this area. This new Translational Center of Excellence (TCE) will investigate innovative immune therapies, particularly design and test new CAR T cell therapies alone or in combination. The TCE will leverage cores at the Abramson Cancer Center, including a human brain tumor tissue bank.

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