$12 Million Multi-institutional SPORE Grant to Focus on Mutations in the NF1 Gene


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D. Wade Clapp, MD

A new, multi-institution research endeavor brings together scientists from nine leading institutions to find treatments for a group of rare cancers, all caused by a particular gene mutation.  

The researchers won a 5-year, $12 million grant through the National Cancer Institute’s (NCI) competitive NCI Specialized Programs of Research Excellence (SPORE) Initiative. The effort, which is led by the Indiana University (IU) School of Medicine and the University of California San Francisco (UCSF), is the first such project to take on a group of cancers linked to mutations in the NF1 gene. It will analyze cancer-promoting signaling pathways and cancer genetics to try to find new effective treatments and drug targets for cancers caused by the loss of NF1 function.

Neurofibromatosis, Ras

Rather than funding studies for one cancer type, the grant takes a new approach by targeting multiple cancers that develop because of NF1 mutations. The mutations cause a genetic disorder known as neurofibromatosis type 1, which frequently develops in children and young adults, and can cause tumors in the skin, nervous system, and blood. The disorder occurs in about 3,000–4,000 people per year worldwide, according to the National Institutes of Health’s Genetics Home Reference.

With the award, researchers will be testing treatments that are designed to block cancer-causing changes that occur because of NF1 mutations. Specifically, they will be testing drugs that block enzyme activities that occur because of abnormal activity of a gene called Ras, which is the most commonly mutated oncogene in human cancers. The NF1 gene normally codes for a protein that helps control Ras. Because NF1 is mutated in people with neurofibromatosis type 1, it leads to uncontrolled Ras activity. Ras, in turn, drives activation of a number of different kinases, which help drive tumor growth.

A technique to determine kinase activities in cells is hoped to help determine how patients respond to different drugs targeting the Ras pathway, as well as to find new clinical drug targets.

Multiple Sites

The trial requires collaboration across multiple institutions because of the rare nature of the disorder. The grant is led by investigators at the Indiana University School of Medicine and UCSF, along with researchers from Johns Hopkins University School of Medicine; the National Institutes of Health; University of Texas Southwestern; Memorial Sloan Kettering Cancer Center; The Children’s Hospital of Philadelphia; and City of Hope National Medical Center.  

“This award is the first Specialized Programs of Research Excellence grant to ever be focused on a series of cancers in a common biochemical pathway, and a SPORE grant focused on orphan diseases in children, adolescents, and young adults,” said D. Wade Clapp, MD, a principal investigator with the project and the Chairman of the Department of Pediatrics at the IU School of Medicine, as well as a member of the IU Melvin & Bren Simon Cancer Center and the Herman B. Wells Center for Pediatric Research. “This SPORE is by design multi-institutional, because of the rare nature of this disease.”  ■

 



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