Worldwide Defeat GBM Consortium
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.
With joint forces from several leading cancer research organizations, NFCR and its global partners established the Worldwide Defeat GBM Consortium—an international collaboration program which involves top cancer researchers from China, US, UK, Germany, Brazil, Singapore, and Australia to work together and develop effective therapies for GBM.
The Consortium has planned to conduct international multi-center clinical trials for testing novel treatment strategies for GBM. Phase I clinical trials will soon begin in cancer centers in both U.S. and China to investigate if a therapy that combines Mammalian Target of Rapamycin (mTOR) inhibitors 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 cancer centers 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 the Worldwide Defeat GBM Consortium, and NFCR has been and will be playing an critical role in this global collaborative effort. By combining international resources and research strengths from different countries, we will reach our goal to defeat GBM and save lives of GBM patients around the world.
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 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 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.