July 12, 2001 PITTSBURGH, July 12 - The University of Pittsburgh Cancer Institute (UPCI) has received a five-year, $12 million Specialized Program of Research Excellence (SPORE) federal grant to examine innovative detection and treatment strategies designed to improve survival outcomes and quality of life for patients with early- to late-stage lung cancer. The grant, awarded by the National Cancer Institute (NCI) to only six centers nationally, attests to the status of UPCI's Lung Cancer Center as a premier center for translational research approaches to the prevention, screening and treatment of lung cancer. The SPORE award will allow UPCI to employ the newest diagnostic tools and bring the latest treatments to patients treated at its Lung Cancer Center.
"We are quite pleased that NCI has recognized UPCI's excellence in basic and clinical lung cancer research through the awarding of this grant. We expect that the results of the research funded through this SPORE will have an unparalleled impact on the way lung cancer is treated in the future and on our understanding of differences among people in their susceptibility to the development and progression of lung cancer," stated Ronald B. Herberman, M.D., director of UPCI and associate vice chancellor for research, health sciences at the University of Pittsburgh.
This is the first SPORE awarded to UPCI in any cancer research area. Since the inception of the award in 1992, a total of six SPOREs in Lung Cancer have been awarded nationally by NCI. UPCI joins other Lung Cancer SPORE awardees including Vanderbilt-Ingram Cancer Center, Johns Hopkins University and M.D. Anderson Cancer Center.
According to Joel Greenberger, M.D., professor and chairman of the department of radiation oncology and co-director of the Lung Cancer Center at UPCI, "We believe many of the studies funded through this grant will soon have direct applicability to patient care. Through the collaborative efforts of UPCI researchers in the laboratory and clinic, the quality of life for lung cancer patients will be enhanced and their prognoses will improve."
The grant funds three major translational research projects, among others, that focus on the mechanisms that increase the susceptibility of women to lung cancer, the use of gene therapy as a protective agent during radiation therapy and the use of CT (computed tomography) in the early-detection of lung cancer.
In the first major project, Jill Siegfried, Ph.D., principal investigator on the grant, professor of pharmacology at the University of Pittsburgh and co-director of the Lung Cancer Center, will examine the gastrin-releasing peptide receptor - a gene linked to abnormal cell growth in the lung that appears to be more active in women than men. Previous research conducted at UPCI has indicated that the gene may be regulated by estrogen and nicotine, and may be a way to explain why women are more likely to develop lung cancer than men, even when they are nonsmokers or smoke less than men. The goal of this project is to determine how tobacco exposure and hormones contribute to the expression of this gene and to examine the expression of four other genes that may contribute to lung cancer risk in women.
Dr. Siegfried will also examine the role of estrogen in the development of lung cancer. The study will examine whether estrogen acts as a proliferation agent in the lung, activating lung cancer development. In addition to examining estrogen's role as a lung cancer proliferation agent, Dr. Siegfried will evaluate anti-estrogens that may inhibit the effect of estrogen on lung tumor growth in women and determine which are the most effective at blocking the action of estrogen in the lungs.
"There has been a lack of research studies on the effects of estrogen on women's risk for lung cancer," said Dr. Siegfried. "By examining an area of research that has been previously understudied, this grant will allow us to learn more about the basic biological factors that may put women at a greater risk for developing lung cancer than men."
Dr. Greenberger will examine the use of manganese superoxide dismutase (MnSOD) plasmid liposome gene therapy as an agent to protect the normal tissues in the esophagus and lung from damage during radiation therapy for non-small cell lung cancer. Damage to normal tissues during radiation therapy has been a major limitation to the effective treatment of lung cancer. The goal of this project is to use MnSOD plasmid liposome gene therapy to prevent the lethal effects of irradiation to the esophagus and normal lung tissue - improving the quality of life for lung cancer patients and potentially allowing for the use of higher doses of radiation or chemotherapy to effectively treat lung cancer without the damaging side effects.
Joel Weissfeld, Ph.D, assistant professor, department of epidemiology and leader of the cancer epidemiology, prevention, and control program, will examine the use of multi-detector CT in the detection of lung cancer. This project's goal is to determine the efficacy of multi-detector CT as a screening tool in detecting extremely small lung tumors that would eventually result in the progression of cancer. If it is determined to be an effective screening tool, patients with extremely small lung tumors discovered by multi-detector CT could be treated early before the cancer has spread throughout the lung or body.
Although often detected at a later stage, earlier detection of lung cancer is extremely important. "Since symptoms do not appear until the disease is well-advanced, successful treatment is dependent on an early diagnosis," said James Luketich, M.D., chief of thoracic surgery and co-director of the Lung Cancer Center. "As a surgeon, I can attest to the importance of developing and examining new methods and techniques for the early detection of lung cancer. When lung cancer is detected at an early stage, minimally invasive surgical techniques can be applied for complete tumor removal in many cases."
In an additional project, Olivera Finn, Ph.D., professor of molecular genetics and biochemistry and leader of the immunology program, will examine the role of the protein Cyclin B1 as an antigen (a substance that causes the immune system to make a specific immune response) and cancer vaccine for non-small lung tumors. Dr. Finn will examine the differences in the expression of Cyclin B1 in normal cells and lung tumor cells to determine what makes Cyclin B1 a tumor antigen.
Despite an overall decline in smoking rates, lung cancer persists as the leading cause of cancer deaths in the United States. Cigarette smoking is by far the most important risk factor for lung cancer. According to the American Cancer Society, an estimated 169,500 people in the United States will be diagnosed with lung cancer this year and 157,400 lung cancer-related deaths are expected to occur. Current treatment for lung cancer results in a five-year survival rate of only 14 percent.
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