The Future of Brain Tumor Therapy

A little over a year ago,  the announcement that Senator Ted Kennedy was diagnosed with a malignant brain tumor brought a lot of attention to brain cancer research. Brain cancers are among the most perplexing types of cancers. Indeed, until now, it was not even known how brain cancers form. It was believed for many years that brain tumor metastasis, or the process whereby cancerous cells move from the location where a tumor has initially grown and spreads to other parts of the body, was the product of “brain-specific homing” of metastatic cancer cells from other areas of the body, followed by direct interactions of the cancer cells with neural tissues. However, recent research from Oxford University, published in the journal PLOS One, demonstrated that metastatic cancer cells in mouse and human tissue utilized “vascular cooption” for seeding brain tumors rather than invading and growing within the neural tissue. What this means is that cancer cells enter blood vessels, where they can then be transported throughout the body. This information is not new. What the Oxford researchers, led by Professor Ruth Muschel, showed is that once in the blood vessels, cancer cells can establish residence and begin to grow along the blood vessel walls. By thus co-opting blood vessels in the brain, tumors can utilize readily available nutrients and oxygen from the blood without having to grow their own blood vessels, which occurs via processes known as neovascularization and angiogenesis.

The normal course of treatment for malignant brain tumors is radiation and chemotherapy. The ability of newly established tumors to utilize existing vasculature may account for the resistance of some brain tumors to many chemotherapy drugs that target neovascularization and angiogenesis. Drug resistance, in part, leads to the poor prognosis for patients with malignant brain tumors. Because existing treatments are largely futile, novel therapies are always being investigated. The research of Dr. Muschel and her colleagues not only identified a novel mechanism of tumor metastasis to the brain, but also identified the integrin family of cellular adhesion proteins as the key molecules that mediate attachment of metastatic cancer cells to blood vessel walls. This discovery could, potentially, lead to novel brain tumor therapies.

Another novel therapy, which I have had the opportunity to work with, is the oncolytic virus, vesicular stomatitis virus (VSV). As a graduate student, I worked with a mutant VSV that had a preference for infecting and killing tumor cells, while sparing normal cells. A primary application for oncolytic VSV is in the treatment of brain tumors, because VSV naturally targets the brain. Many studies have successfully demonstrated the ability of VSV to kill brain cancer cells in vitro and in mouse models. To my knowledge, these studies have not been extended to human clinical trials, but the last I heard they were very close. Similar oncolytic (meaning they “lyse” or kill tumors) viruses have moved into clinical trials, with varying levels of success. Novel therapeutics such as oncolytic viruses, gene and cell therapies and immunotherapies offer the greatest promise for treatment, and potentially even cures, of some of mankind’s deadliest and most debilitating diseases. While these therapeutics are still met with some disdain in the United States (because genetically modified organisms are categorically evil!), other parts of the world are embracing them. These therapies are continuously being shown to be both safer and more effective than traditional therapies. While more research is certainly needed, the potential remains for these therapies to change the face of modern medicine.

Citation: Carbonell WS, Ansorge O, Sibson N, Muschel R (2009) The Vascular Basement Membrane as “Soil” in Brain Metastasis. PLoS ONE 4(6): e5857. doi:10.1371/journal.pone.0005857