May 2001

From Vanderbilt University Medical Center

Grant accelerates race for lung cancer cures

NASHVILLE, Tenn. - The Vanderbilt-Ingram Cancer Center has received a coveted award that recognizes its expertise in lung cancer research and that will fuel its aggressive efforts to develop cures for the leading cancer killer.

The grant, providing $13.7 million over five years, establishes a Specialized Program Of Research Excellence (SPORE) in Lung Cancer, one of only six such programs in the country and the only one in the southeast.

"This is an effort by the National Cancer Institute to pull multiple projects together that focus on a particular cancer tissue site," said Dr. David P. Carbone, Ingram Professor of Cancer Research and director of the SPORE. "These grants are awarded to institutions with a critical mass of experienced investigators in a field. The cornerstone of the work has to be translational research. You have to have both excellent science and excellent clinical translation of that science to patients."

Among the most significant benefits to SPORE funding is that its use is very flexible, Carbone said. Each year, investigators submit reports of their work and progress, but they have the ability to expand, contract, eliminate or add projects as developments warrant. "This gives us the flexibility to rapidly respond to the most promising projects and make the most of the research," Carbone said.

Lung cancer remains the leading cause of cancer death in both men and women in the United States. With an estimated 170,000 new cases each year, lung cancer represents 13 percent of cancer diagnoses. But it kills more than 157,000 Americans each year, accounting for 28 percent of all cancer deaths.

Vanderbilt-Ingram's SPORE will focus on a variety of approaches, from basic research to understand the fundamental genetic and other mechanisms that allow lung cancer to develop and spread, to clinical trials of new treatments, to population-based studies to discover new information about reducing lung cancer risk.

First-year funding will support six scientific projects and four resources that are shared among the SPORE investigators - administration, tissue, biostatistics and clinical core facilities. Carbone directs the administration core; Dr. Alan Sandler, the clinical core; Dr. Joyce Johnson, the tissue core; and Yu Shyr, Ph.D., the biostatistics core.

The grant also provides for career development and pilot projects, supplemented by Vanderbilt University and Vanderbilt-Ingram Cancer Center. This includes two positions through the Vanderbilt Physician-Scientist Development Program, with additional University and Cancer Center funding earmarked for two more positions in lung cancer. Funding is available for three pilot projects, at $50,000 each, with Vanderbilt-Ingram supplementing the work with support for an additional pilot.

The initial year's scientific projects are: Project 1, led by Lynn Matrisian, Ph.D., chair of Cancer Biology and Ingram Professor of Cancer Research, will focus the contribution of metalloproteinases (MMPs) in small cell and non-small cell lung cancer.

This will build on Matrisian's research on the role of MMPs (which "eat" through the matrix between cells) in the spread of tumors. The project will include testing in animal models of drugs that inhibit MMPs.

Project 2, led by Carbone, will use DNA microarray to develop "molecular fingerprints" of lung cancers. Using hundreds of samples over a number of years, the goal is to identify patterns of gene expression that correlate with cancer stage, response to treatment, outcome, and metastasis.

Project 3, led by Dr. Thao Dang, assistant professor of Medicine, and Carbone, will build on their earlier work that implicated a novel gene, NOTCH 3, in lung cancer development.

The SPORE project will further investigate the gene's role in lung tumors using animal models and drugs that inhibit the gene's activity. In addition, the investigators will study human tumor samples for overexpression of the gene.

Project 4, led by Dr. Dennis Hallahan, professor and chair of Radiation Oncology, and Dr. Hak Choy, professor of Radiation Oncology, includes two clinical trials of radiation therapy in combination with "angiogenesis inhibitors," agents that block the development of new blood vessels.

The trials will test a new agent that blocks the vascular endothelial growth factor (VEGF) along with radiation, a combination that earlier work suggests creates a synergistic anti-tumor effect.

Project 5 will examine the role of the enzyme COX-2 (cyclooxygenase-2) in lung cancer tumor development and will study the effect of drugs that inhibit COX-2, both alone and in combination with chemotherapy. Dr. David Johnson, Vanderbilt-Ingram's deputy director, will lead this study along with Dr. Raymond DuBois, associate director of Cancer Prevention, and Dr. Jason Morrow, professor of Medicine.

This work builds on research by DuBois and his colleagues into the important role of COX-2 in cancer development, particularly colorectal cancer. This research has also found COX-2 levels to be elevated in lung cancer as well.

Project 6, led by Dr. Wei Zheng, professor of Medicine, along with Drs. Walter Smalley, associate professor of Medicine, and William Blot, professor of Medicine, includes population-based studies to correlate long-term usage of non-steroidal anti-inflammatory drugs, like ibuprofen, with risk of lung cancer.

The theory to be tested is that, as with colorectal cancer, lung cancer risk will be lower in people who take NSAIDs over long periods of time. NSAIDs exert their influence on pain and inflammation by blocking the activity of COX-2.

The Vanderbilt-Ingram Cancer Center is the only Comprehensive Cancer Center designated by the National Cancer Institute in Tennessee, and one of only 39 nationwide. This designation, the highest ranking awarded to cancer centers by the world's foremost authority on cancer, recognizes research excellence in cancer causes, development, treatment and prevention, as well as a demonstrated commitment to community education, information and outreach. To learn more about the Vanderbilt-Ingram Cancer Center, please visit http://www.vicc.org












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