Posted on September 12, 2002 at 10:37 a.m.

BIRMINGHAM, AL — The University of Alabama at Birmingham (UAB) has received one of the first two Specialized Programs of Research Excellence (SPORE) grants awarded by the National Cancer Institute (NCI) for brain cancer research. The five-year, $13 million SPORE grant is part of a program by NCI to accelerate the translation of laboratory findings into therapeutic applications. The NCI is an arm of the National Institutes of Health.

With the addition of the brain cancer SPORE, UAB and its Comprehensive Cancer Center now hold three of the prestigious SPORE grants. The other SPORE grants are for breast and ovarian cancer. Only two other institutions in the nation have more; Johns Hopkins University has five SPORE grants and the MD Anderson Cancer Center has four. The University of California at San Francisco received the other brain SPORE.

“Since its inception, the SPORE program has contributed to major advances in our understanding and treatment of many cancers such as breast, lung, prostate and ovarian cancer,” says Dr. Albert LoBuglio, director of the UAB Comprehensive Cancer Center. “It is an honor and a testament to the quality of UAB’s neuro-oncology research efforts that we should be the first to receive a brain cancer SPORE grant.”

Dr. Steven Rosenfeld, professor of neurology and director of UAB’s Brain Tumor Treatment and Research Program, is the principal investigator on the new SPORE grant. He says the grant will fund five research initiatives and five core facilities: a brain tumor tissue core, a clinical core, an administrative core, a biostatistics core and an animal models core.

“We’re going to be changing the way we treat this disease and people who get a diagnosis with a malignant brain tumor now have some reason to be hopeful that treatments or cures are on the horizon,” says Rosenfeld. “I really think we’re going to deliver on that promise.”

The NCI reports that 17,000 new cases of brain tumors are expected to emerge in the United States in 2002 and an estimated 13,100 patients will die of brain cancer this year.

“This is clearly a pivotal time in brain tumor research,” says Rosenfeld. “There has been a very disappointing amount of progress in efforts to help people afflicted with brain tumors, despite more than 30 years of very intensive clinical effort. What has changed in the last five to ten years is an explosion of information about the biology of these tumors.”

The SPORE grant program began in 1992. Today there are 41 SPORE grants distributed among 26 institutions. UAB won the brain cancer SPORE in competition with eight other institutions, including Duke University, Johns Hopkins University, University of California at Los Angeles and the University of Pittsburgh.

The five UAB research projects include:

• Evaluation of the role that cytomegalovirus may play in the formation or progression of malignant brain tumors. Cytomegalovirus is a virus that is distantly related to the viruses that cause mononucleosis and cold sores. Dr. Charles Cobbs, assistant professor of neurosurgery, has made the novel observation that cytomegalovirus infection appears to be associated with malignant brain tumors. While the vast majority of the population has been exposed to this virus, Dr. Cobbs, in association with Dr. William Britt, professor of pediatrics, and Dr. Richard Kaslow, professor of epidemiology, will examine if brain tumors are produced by infection with a particular, rare subgroup of cytomegalovirus, or whether instead certain populations of individuals are particularly susceptible to tumor formation by this virus.
  
  
• A study of how to prevent brain tumors from invading normal brain by manipulating specific signaling molecules that are produced by the immune system. The ability of these tumors to invade normal brain is a feature that makes them particularly difficult to treat. They accomplish this in part by secreting enzymes that dissolve the matrix that keeps normal brain cells connected to each other. Etty N. Benveniste, Ph.D., professor and chair of the department of cell biology, has discovered that production of these enzymes can be blocked with a specific set of signaling molecules produced by the immune system, and in collaboration with Dr. Louis Nabors, assistant professor of neurology, will investigate how to translate this finding into new treatments for brain tumors in the clinic.
  
  
• A study of how brain tumors damage normal brain. Brain tumors invade brain not only by dissolving the matrix that holds brain cells together, but by secreting toxins that kill brain cells directly. These toxins also can cause seizures — a common problem in patients afflicted with this disease — and they are secreted through specific pores in the brain tumor cell membrane. In this project, Harald Sontheimer, Ph.D., professor of neurobiology, will collaborate with Dr. Rosenfeld on developing methods of blocking this process that should ultimately be applicable to patients with brain tumors.
  
  
• UAB has an international reputation in gene therapy, and this will be applied to the problem of brain tumors in a project directed by Donald Buchsbaum, Ph.D., professor of radiation oncology, Yancey Gillespie, Ph.D., professor of neurosurgery, and Dr. James Markert, associate professor of neurosurgery. Gene therapy approaches using a variety of engineered viruses, each designed to specifically kill brain tumor cells, will be combined with novel chemotherapy and radiation therapy approaches to see if this can optimize the use of gene therapy in patients with malignant brain tumors.
  
  
• Brain tumors are remarkably effective at generating their own blood supply, which supports their rapid, uncontrolled growth. This process, called angiogenesis, thus represents a logical target in the development of new anti-tumor treatments. Dr. Candece Gladson, associate professor of neuropathology, will lead a study looking at novel ways of inhibiting angiogenesis. In collaboration with Dr. Louis Nabors, the findings of this study will be used to develop new anti-angiogenic therapies that should be directly applicable to patients.