When I read Dr. Siddhartha Mukherjee’s book The Emperor of All Maladies: A Biography of Cancer, the first thing that came to mind for me was that glioblastoma is the emperor of all cancers.
Why might glioblastoma deserve such a designation? I can think of three reasons: First, it attacks the brain, an organ that defines who we are. Second, it is among the most lethal cancers, with a median survival of slightly more than a year. Third, it is among the most complex cancers; there are vast differences within a single tumor and among tumors from different patients. I believe that if we can tame glioblastoma, we can tame any cancer.
The purpose of this blog is to give you a short introduction to glioblastoma (GBM) and share a glimpse of what researchers are doing to beat it.
Incidence of GBM
GBM is a rare and aggressive cancer, with an incidence of two to three cases per one-hundred thousand people per year For the year 2017, over twelve thousand new cases of GBM are predicted. You may have heard of some recent victims of GBM whose cases made news headlines. Mr. Beau Biden, son of former U.S. Vice President Joe Biden, died of GBM. Brittany Maynard, a young woman who became a leading advocate of the right to die, also had GBM; the story of her experiences brought attention to ineffective treatments. When glioblastoma comes back after surgery, as it did for Ms. Maynard, the available therapies are radiation and chemotherapy. Both are ineffective in treating GBM and have severe side effects; she chose to die rather than undergo them.
GBM diagnosis and treatment
There are no tests for early detection of GBM. By the time a tumor is large enough to cause symptoms (such as headache and seizures), surgery is the only option. However, surgery alone is rarely able to remove all of the tumor because GBM infiltrates the normal brain. Therefore, patients are put on a regimen of radiation and chemotherapy. Whatever treatments a patient receives, GBM nearly always comes back.
Understanding the molecular complexity of GBM
As our understanding of GBM increases, we are growing closer to developing effective therapies to control it. We now have detailed information on the molecular makeup of GBM. In 2013, The Cancer Genome Atlas (TCGA) program published a comprehensive molecular analysis of GBM by examining more than five-hundred different GBM samples. This analysis has revealed extensive heterogeneity among GBMs; we now know that GBM cells in different patients use different pathways to grow, so one or two drugs will not be enough to help everyone. We will have to develop a large arsenal of drugs (perhaps as many as twenty) that can block each and every growth pathway that GBM uses. We will then be able to use the precision medicine approach, which is to treat each patient based on the pathway or pathways that patient’s particular GBM uses for its growth.
A new therapy approved by the FDA
In 2015, the FDA approved a new approach for use in conjunction with radiation and chemotherapy. A Tumor Treating Fields device called OPTUNE delivers alternating electric current to the tumor, resulting in the disruption of the tumor’s cell division. You can learn more about this innovation by visiting OPTUNE’s website. It is clear that this approach helps GBM patients. However, future research will determine whether some patients are more responsive to this therapy than others.
New therapies under development
Precision medicine will require us to develop targeted therapies based on identifying a specific pathway involved in tumor growth and then blocking this pathway with a specific drug. One pathway involved in the growth of 40-50 percent of GBM tumors is connected with epidermal growth factor receptor (EGFR), a protein present on cell membranes that relays growth signals. The EGFR in GBM has several abnormalities. One type of EGFR present in over 20 percent of GBM patients is EGFRvIII. My laboratory is targeting EGFRvIII with AZD9291, a drug recently approved by the FDA for lung cancer patients whose tumors carry a specific mutation of EGFR. The data that we have obtained from testing AZD9291 in preclinical models of GBM looks very encouraging, and we plan to initiate its testing in GBM patients very soon. Investigators are also targeting other GBM growth pathways, such as Akt. Future studies will combine targeted therapy with immunotherapy, so that effective treatments are developed for a larger population of GBM patients.
Several groups of researchers are developing oncolytic viruses to destroy GBM. In this approach, the virus kills the tumor cell, and the resulting cellular debris stimulates the immune system to destroy tumor cells. The viruses currently being used in GBM research include the cold virus, herpes virus, and polio virus. All of these therapies look promising, but whether every type of GBM tumor will respond to these viruses needs to be determined.
Dendritic cell immunotherapy
Northwest Biotherapeutics, a biotechnology company that seeks to create personalized cancer vaccines, is working on dendritic cell-based immunotherapy to fight GBM. This therapy is very personalized. Dendritic cells, which are part of the immune system, from the patient are isolated and exposed to the patient’s tumor in the lab. After exposure, the patient’s dendritic cells are injected back into the patient. The company has tested this therapy, known as DCVax therapy, in 331 newly diagnosed GBM patients, and the final results should be available soon. For more information, visit the Northwest Biotherapeutics website.
I hope you have found this blog useful. The message I want to leave you with is that beating GBM is within our reach. If you have any questions or comments, please feel free to contact me:
Madan M. Kwatra, PhD
Further information on GBM
If you’d like to learn more, reliable information on GBM can be obtained from several sources, including: