October 6, 2010
As part of a national effort to accelerate the identification and testing of new anticancer drugs, SAIC-Frederick, Inc., a prime contractor to the National Cancer Institute has awarded two contracts totaling $2.4 million to two teams of UNC scientists to initiate the discovery of drugs for the treatment of childhood leukemia and brain tumors.
• Center for Integrative Chemical Biology and Drug Discovery
Stephen Frye, PhD, professor of medicinal chemistry and director of the UNC Center for Integrative Chemical Biology and Drug Discovery in the UNC Eshelman School of Pharmacy, is principal investigator. Frye is also a member of UNC Lineberger Comprehensive Cancer Center. The two centers are collaborating on both projects.
These contracts, called task orders, were awarded in support of the NCI’s Chemical Biology Consortium program, and provide funding to one-year and eighteen-month milestones respectively. Further funding may be awarded depending upon progress.
“These studies build on research pioneered at UNC Lineberger and already underway in the Integrative Chemical Biology Center, initially with support from the University Cancer Research Fund. Childhood cancers and brain tumors are challenging to treat, and we hope that our work can lead to improved therapies,” Frye says.
In the childhood cancer, acute lymphoblastic leukemia, a protein called mer is abnormally expressed, making the cancer resistant to current therapies. Mer was initially discovered at UNC in the lab of Shelley Earp, MD, UNC Lineberger’s director. UNC scientists will develop selective small molecules inhibitors of mer kinase as drug candidates to treat pediatric ALL. They will also use the molecules as probes to further explore the mechanism whereby Mer activation sustains the survival of lymphoid and other tumors that express mer, potentially opening doors to new treatments for other cancers. The team will collaborate with Doug Graham, MD, a pediatric oncologist at the University of Colorado who was a student of Earp’s and codiscoverer of Mer kinase.
A second project also targets a specific gene involved in gliomas, the most common type of brain cancer. Glioblastoma multiforme, known as GBM, is the most aggressive tumor subtype where fewer than 10 percent of patients survive beyond one year. This research will target the protein product of a gene called IDH1 that is frequently mutated in gliomas. The role of IDH1 in this cancer has been defined through the work of Yue Xiong, PhD, Kenan Professor of Biochemistry and Biophysics and a UNC Lineberger member. The mutation offers a highly specific target for the discovery and development of anti-GBM drugs.
“We were pleased that UNC was selected as one of NCI’s centers when the program was initiated last year and even more pleased that we have received two awards in this highly-competitive process,” said Robert Blouin, PharmD, dean of the UNC Eshelman School of Pharmacy.
Other UNC faculty collaborating on the project include: Gary Johnson, PhD, professor and chair of pharmacology, and Bill Janzen, research professor of the practice; Dmitri Kireev, research professor; and Xiadong Wang, PhD, research assistant professor; all from the UNC Eshelman School of Pharmacy. Janzen, Kireev, and Wang are members of the UNC Center for Integrative Chemical Biology and Drug Discovery.
This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
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