KU researcher awarded NCI grant to investigate ovarian cancer treatments


LAWRENCE – A University of Kansas researcher has been awarded a grant from the National Cancer Institute to conduct ovarian cancer research.

Jennifer E. Golden, a medicinal chemist and assistant director of KU's Specialized Chemistry Center, has received a two-year, $370,000 grant to investigate the use of R-ketorolac – a component of an already approved anti-inflammatory drug – against ovarian cancer.

Golden and her research partners at the University of New Mexico Cancer Center will investigate whether R-ketorolac is capable of inhibiting specific pathways of GTPases, the chemical switches in cells that regulate their behavior and are crucial to cancer proliferation.

"We know that some nonsteroidal anti-inflammatories, or NSAIDs, help combat cancer," Golden said. "But we don't know how or why they work. In other words, we don't know the underlying mechanism that makes them effective in fighting cancer. Our research will focus on R-ketorolac in one potential mechanism involving GTPases."

R-ketorolac is a component of the drug Toradol, a widely used NSAID prescribed to relieve pain after surgery. Thus, Golden's focus on R-ketorolac is a prime example of "drug repositioning" – the art of finding new therapeutic uses for drugs that have already been approved by the FDA – which enables researchers to avoid the incredibly long and expensive process of getting a new drug approved.
"One of the reasons this line of research is so exciting is that R-ketorolac has already been approved by the FDA, meaning it's been deemed safe and effective," Golden said.

"So if our research shows that R-ketorolac derivatives are effective at interfering with how cancer spreads by this mechanism, it will provide insight on why some NSAIDs have anti-cancer capabilities and could allow new cures and therapies to get to cancer patients quicker than if we had to get approval for a brand new drug."

The grant is awarded jointly to Golden, along with University of New Mexico Cancer Center researchers Angela Wandinger-Ness, professor of pathology, and Laurie Hudson, professor of pharmaceutical sciences. The collaboration brings together Wandinger-Ness's work on GTPases, Hudson's research on how ovarian cancer spreads and Golden's medicinal chemistry expertise.

The joint KU-UNM grant comes from the NCI's Provocative Questions Project, which seeks to address 24 designated questions designed to stimulate cancer research in especially effective and imaginative ways. Golden's proposal addresses Provocative Question No. 5 on the list.

Golden's grant is KU's first major NCI grant since the KU Cancer Center was awarded NCI designation this summer.

"This research will enable us to pursue better treatments and cures for individuals with ovarian cancer," Golden said. "I'm so proud to be at a university like KU that continues to demonstrate leadership in cancer research."

Ovarian cancer is the fifth most common cancer among women and causes more deaths than any other type of female reproductive cancer.

Golden, a former KU Self Fellow, earned her doctorate in medicinal chemistry in 2002 at KU. After completing a postdoctoral appointment at Stanford University, she joined Amgen in Thousand Oaks, Calif., where she carried out drug discovery research. Golden joined the KU SCC in 2008 as its assistant director, where she directs research projects involving cancer intervention, infectious disease and neurological disorders.

The KU SCC is a member of the National Institutes of Health Molecular Libraries Probe Production Centers Network, whose mission is to develop small molecule probes and leads based on hits uncovered in NIH screening efforts. The KU SCC collaborates with investigators by providing synthetic and medicinal chemistry resources, informatic analyses of biological data sets and performing structure-activity relationship studies. These partnerships have produced new scientific probes, patents and publications spanning a diverse array of biological targets of therapeutic significance.


Tue, 09/18/2012

author

Joe Monaco

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