INDIANAPOLIS — The Indiana University School of Medicine has been selected to lead a five-year, $12 million national research project to develop new treatments for diseases of a genetic mutation that leads to disfiguring and life-threatening tumors and other developmental disorders, mainly in children.
The grant, one of the highly competitive and coveted projects funded by the National Cancer Institute’s Specialized Programs of Research Excellence initiative, is the first such SPORE grant to focus on pediatric cancers.
“This grant enables us to engage in research from the basic science lab to clinical trials to discover new treatments for a broad range of devastating cancers and related disorders, drawing on a team of some of the finest researchers in this field across the country,” said D. Wade Clapp, M.D., chairman of the Department of Pediatrics at the IU School of Medicine and a member of both the IU Melvin and Bren Simon Cancer Center and the Herman B Wells Center for Pediatric Research.
Dr. Clapp, who will serve as the corresponding principal investigator for the new project, said the funding will enable researchers to determine the complete genetic sequence of the research participants, providing unique opportunities to design precise treatments for patients, to adopt new research techniques and better understand how tumors develop resistance to drugs.
The disease at the heart of the project is neurofibromatosis type 1, which affects 1 in 3000 children and is the most common inherited syndrome causing a predisposition to cancer. Neurofibromatosis is more prevalent than cystic fibrosis, Duchenne muscular dystrophy and Huntington’s disease combined, according to the Children’s Tumor Foundation.
The mutation in the NF1 gene leads to a variety of symptoms, from mild to severe. Patients can develop café au lait spots and disfiguring tumors on or just under the skin. Internally, tumors can develop along nerve tissue and cause problems if they begin to press against vital organs or the windpipe. Some patients suffer from chronic pain.
In addition, recent research has found NF1 mutations in a variety of other types of cancers. NF1 mutations also affect an important molecular signaling protein called Ras, which, Dr. Clapp noted, is involved with more than a third of all cancers. In the process of developing better treatments for those with NF1 disorders, the research should also point the way toward new therapies for many other cancers, he said.
Dr. Clapp and colleagues at IU have been leaders in neurofibromatosis research, having first reported in 2008 that the drug Gleevec appeared to be the first effective treatment for neurofibromatosis type 1 tumors. Subsequent research substantiated that finding, but also determined that in some patients genetic factors and tumor resistance hampered Gleevec’s effectiveness.
The National Cancer Institute’s Specialized Programs of Research Excellence, generally known as SPORE, are highly competitive grants awarded to projects that assemble research activities ranging from a better understanding of basic human biology all the way to clinical trials that lead to new treatments.
In addition to researchers from IU, the neurofibromatosis SPORE group — with the acronym DHART SPORE — will include collaborators from the University of California at San Francisco, the National Cancer Institute, the University of Texas Southwestern, Johns Hopkins University, the University of Alabama-Birmingham and the University of North Carolina.