Research on Glioblastoma Multiforme

The Global Brain Cancer Alliance (TGBCA)

Glioblastoma Multiforme (GBM) is the most common and lethal form of brain tumor in adults. There is no effective treatment option for GBM patients, especially for young patients. Less than 10% of GBM patients survive 5 years or longer after diagnosis, while the average life expectancy is only about 15 months.

Brain cancer knows no boundary – it can strike anyone, regardless of ethnicity or nationality.  To defeat this devastating disease also takes united efforts across institutions and countries. 

As a leading non-profit cancer research organization in the United States and worldwide, the National Foundation for Cancer Research (NFCR) is committed to building an international collaboration platform to defeat GBM on a global scale.

With joint forces from leading cancer research organizations around the world, NFCR and its global partners have recently established The Global Brain Cancer Alliance (TGBCA)—a global collaboration platform which brings together top cancer research scientists and institutions from US, Australia, China, Germany and UK.  The Alliance is aimed to accelerate comprehensive understanding of GBM at cellular and molecular levels, engage the best minds possible to shape the direction of GBM research, and ultimately deliver more effective therapies for GBM patients.

As the first step of moving toward defeating GBM, the Alliance has planned to conduct international multi-center clinical trials for testing novel treatment strategies for GBM.  Phase I clinical trials will soon begin in several major cancer centers in both U.S. and China to investigate if a therapy that combines Target of Rapamycin kinase inhibitors (TORKi) with arsenic trioxide (ATO), a type of traditional Chinese medicine, could more effectively treat GBM patients.  The clinical trial protocol has already been approved by the US Food and Drug Administration (FDA). The trial will begin to recruit 40 GBM patients in the U.S. to participate.  Meanwhile, a protocol is currently being developed to conduct a similar phase I clinical trial in China, in parallel with the US trial.  Data from these trials will be compared to obtain more insights into the molecular features of GBM in patients from different geographic regions and genetic backgrounds.

The clinical trials planned and designed in the US and China are just the beginning of a global research effort on GBM initiated by TGBCA and NFCR will continue to play a critical role in this global collaboration initiative. By combining resources from top research institutions around the world, TGBCA is accelerating GBM research and its translation to patient-benefiting clinical applications.  Our ultimate goal is to defeat GBM and save more lives.

Additional NFCR-funded GBM Research Projects

GBM is challenging to treat because the tumors rapidly become resistant to therapy. As cancer researchers are learning more about the causes of tumor cell growth and drug resistance, they are discovering molecular pathways that might lead to new targeted therapies to potentially treat this deadly cancer.

Discovering Genes to Improve Treatment Efficacy

Webster Cavenee, Ph.D.
Ludwig Institute for Cancer Research, CA

NFCR Fellow Dr. Webster Cavenee is a pioneer in our understanding of the role that hereditary predisposition plays into the development of cancer. His research provided the first genetic evidence for the existence of tumor suppressor genes, which is considered one of the most influential breakthroughs in cancer research. Currently Dr. Cavenee and his co-scientists are exploring new approaches to treating glioblastomas more effectively. They discovered that combining inhibitors of the mTOR molecular pathway and low-dose arsenic in tumor models yielded a synergistic effect, with massive tumor cell death along with very significant shrinkage of the tumor and no ill side effects. Their findings suggest a new approach for the potential treatment of glioblastoma. The team is now ready to launch new clinical trials to test this novel approach to treating glioblastoma  in humans.

Drug Development for Brain Tumors

Ronald G. Crystal, M.D.
Weill Medical College of Cornell University, NY

Dr. Ronald Crystal is conducting research in collaboration with Dr. Viviane Tabar at Memorial Sloan Kettering Cancer Center on using the novel approach of recombinant proteins and antibodies to develop gene therapy to convert brain cells into antibody-producing cells. These antibodies will target the cancer cells in glioblastoma, an aggressive and currently incurable type of brain tumor, which is a novel approach for treating glioblastoma and other types of disorders in central nervous system. The researchers at Dr. Crystal’s laboratory have developed strategies and technologies to successfully deliver genes to the cells in central nervous system, and this research will allow the technology being used for cancer treatment.

Technology Platform for Early Cancer Detection

James P. Basilion, Ph.D.
Case Western Reserve University, OH

Research has shown that brain cancer cells tend to over-produce certain “combinations” of cancer-causing molecules or biomarkers on their cell surface that, together, cause the early progression of abnormal cell growth. NFCR supported scientist James Basilion, Ph.D., is developing the next generation of highly sensitive imaging technology — called molecular imaging—that may produce a visual record of the collection of these early biomarkers on the whole surface of a very small tumor.

To image multiple biomarkers on the whole surface of a living tumor, the Basilion team at Case Western Reserve University has generated a powerful reporter probe, known as Beta Gal. The scientists have engineered Beta Gal to bind to biomarkers on living cancer cells and immediately generate a signal that “reports” the presence of the biomarkers, creating an image that can be captured by a camera.

This platform technology has the potential to enable doctors to detect brain and many other cancers at their earliest stage. What’s more, it will provide clinicians with improved accuracy compared to existing detection methods which only sample small areas of tumors from biopsy and thus tend to yield only partial information. This unique advantage of molecular imaging holds great promise for the detection of brain cancer and other types of cancer — at their earliest stage — when patients can be most effectively treated.

Refining the Treatment Strategy

Rakesh Jain, Ph.D.
Massachusetts General Hospital, MA

In recent years, new therapeutic approaches directed at the blockade of the vascular endothelial growth factor (VEGF) pathway have yielded encouraging results in recurrent GBM. As a result, the FDA approved bevacizumab (a VEGF-specific antibody, Genentech) for brain tumor treatment in 2009. Unfortunately, the benefits of anti-angiogenic therapy are transient. Bevacizumab recently failed to prolong survival of newly diagnosed GBM patients when combined with chemo-radiation therapy.

World-renowned NFCR supported scientist on angiogenesis, Dr. Rakesh Jain, and his team of researchers at Massachusetts General Hospital have studied over the last 11 years the effects of VEGF inhibitor in brain tumors in laboratory experiments and in clinical trials. Recently, with NFCR funding, Dr. Jain’s team has shown that anti-VEGF inhibition may transiently “normalize” the structure and function of tumor vasculature, alleviate cerebral edema, and prolong survival in a sub-set of patients. They have also shown that the measuring the extent of this vascular normalization by imaging and proteomic techniques might help identify which patients will benefit from anti-angiogenic treatment. The results of their research were published in the Proceedings of the National Academy of Science (PNAS) Early Edition. Click here to read more.