BACKGROUND AND CHALLENGES

Primary brain cancers pose immense challenges for effective treatment. The most common form of brain cancer in adults is glioblastoma, which originates from glial cells, the non-neural supportive cells in the brain. Glioblastoma is extremely aggressive. Malignant tumor cells readily invade and migrate locally and blend with neighboring normal brain tissue, causing damage to critical neural functions and often leading to lethal tumor recurrence. In 2009, new diagnoses of primary cancers in the brain or nervous system in the U.S. were estimated at nearly 22,000 and approximately 13,000 lives were lost to these types of cancer.

Fortunately, the death rate from primary brain cancers has decreased somewhat over the past three decades in the U. S., thanks to progress made in the treatment of this disease. Still, only about one out of every three patients with primary brain cancer will survive longer than five years after initial diagnosis. Further improvement in survival rates for brain
cancer patients requires more effective therapies.

Recognizing the urgency of the situation facing brain cancer patients, the National Foundation for Cancer Research funds leading cancer researchers who are seeking a deeper understanding of the molecular mechanisms of brain cancers, with a special emphasis on translating these research discoveries into new, and hopefully more effective, therapies for these patients. Below are four examples of the innovative brain cancer research programs that the National Foundation for Cancer Research currently supports.

TRANSLATING RESEARCH INTO THERAPY:

A new targeted therapeutic agent to treat highly aggressive brain tumors is now in Phase I clinical evaluation thanks to the work of NFCR Scientist Webster K. Cavenee, Ph.D., at the Ludwig Institute for Cancer Research in San Diego. Dr. Cavenee's team had previously discovered that a mutated version of the protein Epidermal Growth Factor Receptor (EGFR), named EGFRvIII, is strongly associated with rapidly progressing tumors such as glioblastomas. His research team has now developed an antibody that specifically targets EGFRvIII on cancer cells and turns off the tumor growth signal
emitted by the mutant protein. The results of the Phase l clinical trial on glioblastoma patients are very encouraging:  the antibody has been shown to target and concentrate in the brain tumors and the treatments produce few significant side effects in patients. This novel targeted drug may bring new hope to patients suffering from glioblastoma. Dr. Cavenee is currently trying to combine this new drug with other therapeutic agents to generate enhanced treatment efficacy for brain cancer patients.

Improving surgical outcomes with advanced molecular imaging technology.  Directed by James Basilion, Ph.D., the NFCR Center for Molecular Imaging at Case Western Reserve University aims to develop advanced molecular imaging technology for early cancer diagnosis and improved treatment. Recently, Center researchers have developed new technology that uses tumor biomarkers to identify infiltrating cancer cells from highly aggressive glioblastomas during surgery, providing important assistance in improving surgical removal of tumor tissue. Further enhancements to this technology by Dr. Basilion and Center researchers may lead to better outcomes for patients with this very
aggressive type of brain tumor.

Tailoring a new anti-cancer drug to the right patients. CloretazineTM is a new anti-cancer drug designed by NFCR Scientist Alan Sartorelli, Ph.D., from Yale University School of Medicine. Cloretazine is currently being evaluated clinically in patients with brain tumors and other types of cancer. However, results from earlier clinical trials involving leukemia patients as well as laboratory work with human brain tumor samples suggests that Cloretazine is unlikely to bring uniform benefits for all brain tumor patients in the trial. Consequently, understanding how to predict which patients are most likely to benefit from treatment with Cloretazine has become one of the most vexing questions facing the clinicians treating those patients.  At the molecular level, Cloretazine works best in tumor cells which contain low levels of a protein called AGT. Because AGT levels vary greatly in individual patients' tumors, a reliable method of measuring the level of AGT in tumor tissue would greatly help physicians to predict which patients will likely respond to Cloretazine and those who probably will not. To be clinically applicable, the method must also be both accurate and simple to carry out. Taking advantage of the drug's molecular mechanism, Dr. Sartorelli has recently developed an AGT assay that meets both criteria when tested with tumor cell cultures. Dr. Sartorelli is now further evaluating the AGT assay with human tumor samples, and this new method may soon be used in the clinic, enabling physicians to target the use of this drug to the most appropriate of their brain tumor patients.

Identifying the gene signatures of glioblastoma cells on the run. A hallmark of glioblastoma is the ability of the tumor cells to migrate and invade normal brain tissue. Tumor cell migration and invasion is also a main reason for treatment failure and patient death. NFCR Scientist Stanley Cohen, M.D., at Stanford University School of Medicine, and his research team are studying human glioblastoma cell lines in hopes of gaining a deeper understanding of what keeps these cells on the run. Using a novel approach, the team has identified a 22-gene signature that is correlated to cell migration and invasion of glioblastoma. Importantly, their results in laboratory studies have been confirmed by subsequent studies involving patients' tumor samples. The identification of these genes provides novel molecular targets around which new therapies can be developed - an essential step in preventing the lethal invasion of glioblastoma and saving more lives.

NEXT STEPS: HOW CAN YOU HELP

These research projects hold great promise for developing more effective therapies for brain cancer. With more money, however, they could ramp up their efforts and accelerate progress - and that is what the urgent plight of glioblastoma patients demands. Your contribution  will be directed to these and other life-saving NFCR research initiatives against brain cancer. To donate, click here.