Jill M. Siegfried, Ph.D., co-director of the University of Pittsburgh Cancer Institute's (UPCI) Lung and Thoracic Malignancies Program, has received a $1 million grant from the V Foundation for Cancer Research, an organization founded by ESPN and Jim Valvano, former legendary basketball coach of North Carolina State University. The grant will help support the establishment of new clinical trials for lung cancer patients at the University of Pittsburgh Medical Center's (UPMC) Cancer Centers.

"This award is especially exciting because it supports the translation of our work in the laboratory directly into two separate clinical trials, which we hope will benefit patients," said Dr. Siegfried. "It is particularly gratifying when the work in the laboratory moves from bench to bedside."

The first clinical trial is based on Dr. Siegfried's research, which found that estrogen acts as a proliferation agent in the lung, activating lung cancer development through pathways similar to those in breast cancer. In addition to examining estrogen's role as a lung cancer proliferation agent, Dr. Siegfried evaluated anti-estrogens to see if they could inhibit the effect of estrogen on lung tumor growth in animal models and determined which are the most effective at blocking the action of estrogen in the lungs.

According to Dr. Siegfried, her research demonstrated that it might be possible to inhibit lung cancer tumor growth in cancers that progress in response to estrogen. "We learned that some very basic, biological functions put women at risk for developing lung cancer. Now we know estrogen plays a role in the growth of some lung cancers and that gives us something to target in the clinical setting."

This research was supported by the UPCI Specialized Program of Research Excellence (SPORE) in lung cancer, which is led by Dr. Siegfried. Recent results announced by the Women's Health Initiative in the medical journal The Lancet support Dr. Siegfried's hypothesis: women in that study who took hormone replacement medications containing estrogen were much more likely to die from lung cancer than those who did not. The Lancet publication cited Dr. Siegfried's research as an explanation for the findings.

The clinical trial at UPMC will be led by Athanassios (Ethan) Argiris, M.D., professor of medicine at the University of Pittsburgh School of Medicine, and clinical associate director of UPCI's SPORE in lung cancer. The SPORE is a federal grant awarded by the National Cancer Institute (NCI) to assist researchers in examining innovative detection and treatment strategies designed to improve survival outcomes and quality of life for patients with early to late-stage lung cancer.

According to Dr. Argiris, the phase II trial will study the use of an aromatase inhibitor, a class of drugs designed specifically to counteract estrogen production, in postmenopausal women with advanced non-small cell lung cancer. "We hope that by targeting estrogen we will be able to extend the lives of women with lung cancer. Moreover, we will have an opportunity to understand which women respond best to this treatment by examining the estrogen receptors found in their tumors."

Additionally, the V Foundation will support a phase I trial translated from previous SPORE-funded research conducted by Olivera Finn, Ph.D., professor and chair of the Department of Immunology at Pitt. Lung cancer patients who enroll in the trial will receive a vaccine based on the protein cyclin B1. Dr. Finn discovered that this protein is inappropriately expressed by many lung tumors and causes a strong immune response. She hopes to boost the ability of the immune system to reject lung cancer by vaccination with portions of the purified cyclin B1 protein.

Lung cancer is the leading cause of cancer death in both men and women worldwide. Non-small cell lung cancer is the most common type of lung cancer and represents about 80 percent of all lung cancer cases. Unfortunately, because symptoms don't appear in most patients until the disease is advanced, very few patients survive beyond five years.

Source
University of Pittsburgh Cancer Institute