New Awards from NCI Bring Cancer Research Funding to $28 Million

Program Furthers IITRI's Work in Chemoprevention

The National Cancer Institute (NCI) granted IITRI the second and third of three major awards this spring, topping out at $28 million. The latest awards, announced in May 2004, will fund a series of studies in cancer prevention research.

The first award, announced in April 2004, is a seven-year, $17.3 million contract to advance the development of novel cancer therapeutics. (See related article: IITRI Wins Major NCI Program to Support Development of New Cancer Drugs.)

The new awards, which total $10.8 million, will fund programs in two related areas of cancer prevention research:

• A five-year, $4.5 million program, "Preclinical In Vitro and In Vivo Screening Assays for Cancer Preventive Agent Development," will involve the conduct of early-stage drug discovery studies to identify novel agents for the prevention of cancer in the breast, oral cavity and other sites.


• A five-year, $6.3 million program, "Preclinical Toxicology Evaluation of Chemopreventive Agents," will support preclinical toxicology studies of cancer preventive drugs. Results from these studies will lead to clinical trials with agents showing the greatest potential for success.

All combined, the awards compose the largest IITRI has received for drug development from the National Institutes of Health, the umbrella agency of NCI.

Agents Studied for Chemopreventive Properties

Scientists in IITRI's Toxicology and Carcinogenesis Division will study experimental drugs as well as natural extracts such as isolates from soy beans and green tea for their chemopreventive properties. The challenges include identifying agents that inhibit or reverse molecular alterations that result in the development of precancerous and cancerous cells, and, secondly, determining which of those can attain blood levels that are high enough to be effective without introducing limiting toxicity.

The primary goal of this research is to develop agents that will delay the onset of cancer in high-risk human populations and, ultimately, prevent cancer in specific sites. Toward this end, the program aims to shed further light on the molecular and biochemical mechanisms that are characteristic of cancer cells. By identifying these pathways, scientists can hone in on the means to block them, so as to inhibit or reverse the growth of cancer cells.

IITRI Instrumental in Prevention Breakthroughs

IITRI has been working extensively in cancer chemoprevention since the mid 1970s and has "probably done as many cancer prevention studies as any institution in the world," notes David L. McCormick, Ph.D., D.A.B.T., Vice President and Director of IITRI.

Recent IITRI programs in nutrition have emphasized dietary approaches to prevent prostate cancer. For instance, two different components of soy (Bowman-Birk Inhibitor [a protease inhibitor fraction] and an isoflavone formulation enriched for genistein) have been shown to protect against prostate cancer induction in rats. Similarly, 9-cis-retinoic acid, a retinoid that is the endogenous ligand for the retinoid X receptor, also inhibits prostate carcinogenesis.

Gene Inhibition Shown to Retard Oral Cancer

In another IITRI study, PCR techniques were used to quantify the expression of a small battery of genes that were considered possible mechanistic targets for oral cancer prevention. The scientists identified one gene (cyclooxygenase-2 [COX-2]) that is highly overexpressed in oral cancers induced by 4-nitroquinoline-1-oxide (NQO; 20 ppm).

They also demonstrated that dietary administration of a specific COX-2 inhibitor (celecoxib) and an agent that inhibits both COX-1 and COX-2 (piroxicam) both confer protection against oral carcinogenesis in the rat/ NQO model system. These results suggest that COX inhibition may provide a viable strategy for the prevention of oral cancer in humans.

Future Agenda Targets Key Molecular Pathways

Future programs will involve more extensive integration of molecular biology into studies designed to identify new chemopreventive agents and to characterize their toxicity. Using this approach, both drug discovery and preclinical development of novel agents can be focused on key molecular pathways, with the goal of identifying more active and/or less toxic compounds.

For more information on IITRI's cancer research services, please visit the Carcinogenesis and Toxicology pages of our web site.