Joshua Rosenthal, Ph.D.
Natural products are a leading source of therapeutics—anticancer agents included. For instance, some 60 to 65 percent of all anticancer drugs are derived from natural products. Additionally, sales figures from 2003 show that for all drug sales of more than $1 billion, purely synthetic therapies comprise only 20 percent of the market.
The International Cooperative Biodiversity Groups (ICBGs) program addresses the interdependent issues of drug discovery, biodiversity conservation, and sustainable economic growth. Funding awarded under a program announcement (http://grants2.nih.gov/grants/guide/rfa-files/RFA-TW-04-004.html), which expired in February 2006, is supporting groups that are conducting research on using nature’s diverse resources for drug development. Additionally, this research is focused on maintaining biodiversity and promoting economic growth in countries that have potentially natural-sourced drugs.
Since awards were first made in 1992, ICBGs have conducted research in nine countries in Latin America, Africa, southeast and central Asia, and the Pacific Islands. Some 5,000 species of plants, animals, and fungi have been collected to examine biological activity in 19 different therapeutic areas. Numerous publications in chemistry, biodiversity policy, conservation, and ethnobiology have emerged from the funded investigators, and several plant species new to science and many novel compounds have been discovered.
The program has been re-competed under the updated RFA-08-007 (http://grants.nih.gov/grants/guide/rfa-files/RFA-TW-08-003.html), and awards are expected during 2008. Four governmental agencies are cosponsoring RFA-08-007: National Institutes of Health (NIH), National Science Foundation (NSF), Department of Energy (DOE), and Department of Agriculture (USDA). The participating components of the governmental organizations are: Fogarty International Center (FIC/NIH); National Cancer Institute (NCI/NIH); National Institute of Mental Health (NIMH/NIH); National Institute of General Medical Sciences (NIGMS/NIH); National Center for Complementary and Alternative Medicine (NCCAM/NIH); Office of Dietary Supplements (ODS/NIH); Directorate for Biological Sciences (NSF); Office of Biological and Environmental Research (DOE); and Cooperative State Research, Education, and Extension Service (USDA).
Office of the DTP Associate Director
The process of creating an effective, molecularly targeted cancer drug begins with basic research and the search for chemical compounds with potential anticancer properties and molecules within cancer cells and their surroundings that might provide targets for cancer interventions.
In 2001, NCI began Rapid Access to NCI Discovery Resources, or R·A·N·D, a program to provide DTP resources to academics and nonprofit organizations in the earliest stages of finding promising therapeutics. Recent advances in chemistry, molecular biology, bioinformatics, and high-throughput screening methods have increased the number of agents that can be screened and studied, but they often require a large investment in equipment that most academics cannot afford.
With the help of R·A·N·D, DTP hopes to accelerate the rate at which new compounds are studied for fighting cancer. Examples of preclinical discovery tasks that DTP can provide through R·A·N·D include, but are not limited to:
R·A·N·D is not a mechanism for obtaining grants. To access the contract-based services of the R·A·N·D program, academic and nonprofit researchers can submit applications to DTP twice a year, on April 1 and October 1. The applications, which provide a detailed summary of the proposed project, are reviewed by a panel of extramural experts who assess the strength of the hypothesis, novelty, and cost-benefit ratio. Once an application is accepted, R·A·N·Dservices are performed at no cost to the investigator by DTP contracts. All output from the project is returned to the originator for further investigation. Among the recipients of R.A.N.D services is Dr. Deborah Lannigan, University of Virginia, whose research group is studying the ribosomal S6 kinase (RSK) family, which are downstream effectors of mitogen-activated protein kinase. RSK is overexpressed in about 50 percent of breast and prostate cancers compared to normal tissue. DTP is supporting this research with a high-throughput screening campaign combined with molecular modeling of the active site of the protein.