Today, about 25% of drugs approved to treat cancer are derived from nature – from the bark of a tree to marine life to bacteria in the soil. However, great potential remains in the discovery of natural products with properties that can prevent cancer or treat it early before it spreads. A University of Oklahoma researcher recently earned a National Institutes of Health grant to evaluate thousands of natural products with therapeutic potential.
The grant was awarded to Chinthalapally V. Rao, Ph.D., an OU College of Medicine professor and director of the Center for Cancer Prevention and Drug Development at OU Health Stephenson Cancer Center. Rao brings more than 30 years of experience in studying and refining natural products for drug development. He will coordinate with the National Cancer Institute's National Center for Translational Sciences, which has a repository of approximately 500,000 diverse natural product samples.
A principal objective of the grant is to better understand which specific components of a natural product have anticancer properties and the process by which they produce that effect. Those aims represent a knowledge gap that must be filled in order to increase the use of natural products in drug development.
Currently, we don't have sufficient understanding about how natural products target cancer pathways (how cancer develops and persists). With this grant, we aim to discover the precise target of natural products, and that precise target must be relevant to the progression of cancer."
Chinthalapally V. Rao, Ph.D., Professor, OU College of Medicine
More specifically, Rao and the research team will evaluate natural products for their effect on colon cancer. Because colon cancer grows slowly, it is a good candidate for prevention or early treatment. Rao's research career has largely focused on targeting colon cancer pathways.
"It can take 10 to 15 years for an adenoma (a benign tumor) to progress to a carcinoma," he said. "That's why we have a good chance to prevent or intercept colon cancer."
The natural products will be tested via high-throughput screening, a method used in drug discovery to assess a large number of substances quickly. The process will identify and isolate each natural product's active compounds, setting the stage for more detailed analysis.
The work will be done in collaboration with the Center for Therapeutic Sciences, a drug discovery and development hub on the OU Health Sciences campus. Center director Matthew Hart, Ph.D., will lead the screening of thousands of natural products. High-throughput screening provides "leads" about promising compounds, an important first step in narrowing down the candidates best suited for further study.
Once the process zeroes in on the top candidates, Rao and his team will begin testing them in mouse research models. This will provide information about how well a natural product inhibits tumor growth, the dose that is required for maximum effect, and whether it has any toxicities.
During his career, Rao has identified several natural products that can potentially prevent colon cancer or treat it at an early stage. They include the spice curcumin, caffeic acid esters (derived from honeybees), oleanonic acid (found in many fruit plants) and diosgenin (an herbal plant).
Discovering new approaches for preventing and treating cancer is a key component of the OU Health Stephenson Cancer Center, Oklahoma's only National Cancer Institute-designated cancer center.
"The best way to fight cancer is to prevent it or treat it before it metastasizes," said Robert Mannel, M.D., director of Stephenson Cancer Center. "Natural products hold the potential to be used in drugs that target specific cancers without causing the severe side effects that often come with more traditional therapies. Our research enterprise is well-positioned to study natural products and ultimately create drugs that can be tested in clinical trials."
About the project
The research reported in this news release is supported by the National Cancer Institute, a component of the National Institutes of Health, under award number 1UG3CA290310-01. The project's title is "Discovery and Development of Natural Products for Interception of CRC." Other co-investigators include Venkateshwar Madka, Ph.D., and Nataliya Smith, Ph.D., of the OU College of Medicine. The grant provides nearly $1 million over three years. If the research team meets milestones, they receive another three-year, $1 million grant to continue the work.
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