黑料网 Lineberger Comprehensive Cancer Center researchers and eight other leading cancer research institutions have won a five-year, $12 million grant to try to find treatments for a group of cancers linked to mutations in the NF1 gene.
A new, multi-institution research endeavor brings 黑料网 Lineberger Comprehensive Cancer Center researchers together with scientists from eight other leading institutions to find treatments for a group of rare cancers all caused by a particular gene mutation.
The researchers won a five-year, $12 million grant through the NCI鈥檚 competitive NCI Specialized Programs of Research Excellence initiative. The effort, which is led by the Indiana University School of Medicine and the University of California San Francisco, is the first such project to take on a group of cancers linked to mutations in the NF1 gene. It will take advantage of 黑料网 Linebeger鈥檚 expertise in the analysis of 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.
鈥淭his highly prestigious award links basic science with clinical research to drive new treatment strategies for a range of cancers caused by NF1 gene mutations,鈥� said Gary L. Johnson, PhD, a 黑料网 Lineberger member and the Kenan Distinguished Professor and chair in the 黑料网 Department of Pharmacology. 鈥淭he project will leverage 黑料网鈥檚 demonstrated expertise in chemical proteomics and next-generation genomic sequencing to allow us to better understand, on a molecular level, what is driving these cancers, and how they鈥檙e evading treatment.鈥�
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 to 4,000 people per year worldwide, according to the National Institutes of Health鈥檚 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, Johnson said. The NF1 gene normally codes for a protein that helps control Ras. And 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 proteins called kinases, which help drive tumor growth.
Johnson鈥檚 lab developed a technique to determine kinase activities in cells. The plan is to leverage that expertise 鈥� as well as 黑料网鈥檚 expertise in genomic sequencing 鈥� to determine how patients respond to different drugs targeting the Ras pathway, as well as to find new clinical drug targets.
鈥淲e want to know if these drugs work, and if not, why not,鈥� Johnson said. 鈥淲e will be using DNA and RNA sequencing as well as protein kinase activity analysis to try to accomplish that goal.鈥�
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In addition to Gary Johnson, two other Pharmacology joint faculty members are investigators on the project: David Eberhard, MD, PhD, an associate professor in the 黑料网 Department of Pathology and Laboratory Medicine and a 黑料网 Lineberger researcher; and Shawn Gomez, an associate professor in the 黑料网/NCSU Joint Department of Biomedical Engineering and in the 黑料网 Department of Pharmacology.