Toronto – Canada

 

 

 

 

Text and Photography By James T. Rutka, MD

 

 

Brain Invasion:  Clues From The Leading Edge

 

 

 

In the wake of the passing of Canadian rock icon from the Tragically Hip, Gord Downie, of the malignant brain tumor. glioblastoma, it is timely to reflect on this aggressive and universally fatal cancer that afflicts an ever-increasing number of North Americans each year.  Some of you may remember that glioblastoma is the cancer that claimed the life of U.S. Senator Ted Kennedy.  U.S. Senator John McCain was also recently diagnosed with this tumor.  Interestingly, famed musician George Gershwin died from this cancer at the young age of 38, just shortly after he had written the music for his famed opera, “Porgy and Bess”.

Glioblastoma arises from deranged precursor cells of the glial, oligodendroglial,or neuronal lineages.  The inciting factors leading to the development of glioblastoma are not completely understood, but recent molecular genetic studies have identified alterations in a number of important candidate genes, including the epidermal growth factor receptor, p53, NF1, and IDH1, to name a few.

Glioblastoma is characterized by a highly proliferative central core of cancer cells, and perhaps more importantly, a wave of highly infiltrative cells which invade into normal regions of the brain.  In fact, it is the extensive brain invasion of glioblastoma that makes it such a difficult tumor to treat.

As with most brain tumors, glioblastoma causes neurological symptoms and signs by virtue of continuous tumor growth and mass effect.  The common symptoms and signs of glioblastoma include seizures, personality change, headaches, and weakness of one extremity or sensory disturbance.   These days, the diagnosis is confirmed by brain magnetic resonance imaging (MRI) scanning. 

Treatment of glioblastoma is multi-modal and includes neurosurgical resection of the tumor where feasible, followed by radiation therapy and chemotherapy.  The discovery of the benefit of the drug temozolomide has led to some improvement in overall survival.  A number of other novel therapies are being explored at this time in clinical trials. 

My research laboratory has been dedicated to increasing our understanding of the mechanisms by which glioblastoma cells grow and invade the brain.  While ourexperimental studies are still preliminary, we have identified important signaling pathways which lead to brain invasion.  If these pathways are blocked, we can turn a highly invasive cancer like glioblastoma into a focal tumor which can then be treated more effectively with focal therapy.  New techniques such as MRI-guided focused ultrasound appear quite promising to help us reach the invading glioblastoma cells in the normal brain with improved concentration of targeted chemotherapeutics. 

Kenneth Blanchard wrote, “None of us is as smart as all of us”, and so my hope is that collective efforts to study glioblastoma around the globe will lead in time to more effective therapies for this devastating tumor.

 

 

 

 

 





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