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Au naturel
July 2011
by Lori Lesko  |  Email the author
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JACKSON, Miss.—A new partnership targeted toward discovering natural cancer-fighting drugs has been launched by the University of Mississippi's National Center for Natural Products Research (NCNPR) and the UM Medical Center (UMMC) Cancer Institute.

The collaboration is a natural fit, with the NCNPR pairing its compound-identification and screening expertise with UMMC's Cancer Institute's drug development and clinical-trials capabilities.

The agreement, announced May 17 between the Oxford-based NCNPR and the Cancer Institute in Jackson, creates the Drug Discovery Core, which will be directed by David Pasco, assistant director of the Natural Products Center and research professor in pharmacognosy.

The drug discovery process begins at the NCNPR, where researchers collect plants and other natural products, create extracts and screen them for activity against given targets. The most promising anti-cancer compounds will be further isolated and sent to Jackson for development and testing.

"Our natural products sources and expertise at NCNPR, coupled with the mechanistic evaluations, animal models and clinical capability at the University of Mississippi Medical Center, will give us a discovery and development pathway for natural products based drugs that is fairly unique," says Dr. Larry Walker, NCNPR's director.

The collaboration came together after the arrival of Dr. Lucio Miele as the Cancer Institute director in summer 2009. He has worked to expand the institute's research mission by hiring scientists, purchasing high-tech equipment and forging partnerships with other institutions, according to UMMC. Founding the Drug Discovery Core is a milestone in that effort.

"Development of new anti-cancer agents is one of the most important aspects—if not the most important aspect—of cancer research," Miele says. "The Natural Products Center has tremendous experience and this agreement increases the synergy between our two campuses."

Natural products, he adds, are a rich source of drug discovery and have yielded some of the most potent drugs we still use—the best example being Taxol, a drug that UM researchers had a hand in developing as the NCNPR was first forming.

Cancer research has advanced to the point where scientists have identified most genes and gene mutations responsible for causing cancer. Those are the targets of drug developers.

"There are several hundred genes identified," Pasco says. "But they all belong to about 12 different signal-transduction pathways. Blocking those pathways with specially designed drugs can essentially keep genes from switching on or off."

In Oxford, Pasco and his team finished screening about 30 plant extracts earlier this year that are used in traditional Chinese and Indian medicine, some with proven anticancer properties. The screenings assessed the activity of each extract along the dozen or so pathways, with about 25 extracts showing activity on the majority of the signaling pathways.

Lest the process seem overly simple, think of each pathway as a struck piano key, he says. The note alone may not be significant, but played in sequence with others, it can create an ominous concerto—a tumor.

"Shutting down the concerto requires blocking several pathways at once," he says. "Hence, identifying natural products capable of blocking multiple pathways could be a major step in our quest for better cancer drugs. Specific collections of these pathways are involved in the expression of cancer—and there's a lot of crosstalk among those pathways.

That's what makes cancer so difficult to treat, Pasco notes.

"Once we find an interesting extract, we can tear it down further to get at the active compound," he adds. "Because cancer is so complicated, you need to use a range of compounds to prevent the tumors from becoming resistant to the compounds you're using."

Jack Mazurak of UMMC's Division of Public Affairs says the Cancer Institute will receive candidate drugs—combinations of compounds from the National Center for Natural Products Research—and perform in-vitro tests on various cancer cell lines.

"Once proven in vitro, UMMC Cancer Institute researchers will then test the drugs on tumors in animal models—likely mice or rats—and if successful, move on to clinical trials," he says.

The Drug Discovery Core "encompasses a wide range of development, from isolation of initial compounds on up through human trials," Mazurak says. "The NCNPR is a unique component in itself, allowing the Core to draw candidate compounds from a massive bank of natural-product samples compiled over more than a dozen years. Moreover, the Core is not simply looking for natural products that kill cancer cells. It is using sophisticated assays to screen for natural products that affect specific molecular pathways known to be important to cancer and cancer stem cells."

Rather than seeking new chemotherapy agents, they are seeking targeted pathway inhibitors that can be part of the next generation of cancer drugs, he says.

"While the new Core has the capability to test and develop compounds against a wide variety of cancers, we are focusing now on compounds that will potentially interrupt signaling pathways in solid-tumor cancers, particularly breast, lung and ovarian," Mazurak says. "Much of the Cancer Institute's basic-science research is targeted at those same types of cancer."

In discussing whether the partnership seek a commercial partner, Mazurak said the Core "is certainly open to contract work from the pharmaceutical industry. Also, as our own drug candidates move into the later stages of development, researchers may seek partnerships with industry or find spin-off companies.

"With the Core's potential to create new cancer-fighting drugs, we certainly recognize and invite the possibility of creating local and regional economic growth," he concludes.

 
Code: E071121

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