Investigators at the McArdle Laboratory for Cancer Research pursue a variety of approaches to increase our understanding of the biology and causes of cancer. A few of the recent advances made at the Laboratory, with an emphasis on the potential impact of these results for the treatment or prevention of human cancer, are highlighted below.

Cervical cancer is a major cause of cancer-related mortality among women worldwide. Development of this disease is associated with infection by certain subtypes of human papillomaviruses. Dr. Paul F. Lambert and his colleagues have developed transgenic mouse models for studying the roles of viral oncoproteins in cancer development. Using these animals, they have demonstrated that both the genetic background and immune response of the host play a role in the development of preneoplastic and neoplastic lesions. These findings are exciting because they indicate that the transgenic mice may provide a powerful model for studying the immunobiology of HPV-associated diseases, with the potential of leading to preventative treatments that would decrease the prevalence of cervical cancer.

In addition to its utility as an adjuvant to chemotherapy for breast cancer, the antiestrogen tamoxifen has been proposed as a potential chemopreventive agent for reducing the risk for development of breast cancer. Dr. Henry C. Pitot's observation that this drug may promote the development of other neoplasms and enhance their progression to malignancy argues that healthy women given tamoxifen for the chemoprevention of breast cancer should be monitored closely for their risk for cancer at other sites.

Novel strategies for the chemoprevention of colon cancer are the focus of a collaborative effort between Dr. William F. Dove and members of the UWCCC. Dr. Dove's laboratory has identified and characterized a mutant mouse that provides a model for human familial adenomatous polyposis. Because these animals are at extremely high risk for the development of intestinal cancers and the tumors arise with a predictable time course, the mutant mice are being used to test the efficacy of ornithine decarboxylase inhibitors and non-steroidal anti-inflammatory drugs in preventing or delaying the onset of colon tumors. Dr. Dove's laboratory has also tentatively determined the molecular identity of a gene that acts as an important modifier of colon cancer risk.

Research by Dr. Bill Sugden is focused on the molecular genetics of Epstein-Barr virus, a human pathogenic herpesvirus that is causally associated with several human cancers, including lymphomas and carcinomas.

Dr. F. Michael Hoffmann is working to identify genes that encode proteins on signal transduction pathways. Molecular probes will be used to determine whether changes in signal transduction pathways occur during the development or progression of breast cancer neoplasms. Dr. Janet Mertz and her colleagues have discovered a novel protein related to the estrogen receptor that may cooperate with the estrogen receptor to control gene expression in cells. This finding will have importance in defining effective strategies for the therapy of breast cancer and other hormone-responsive tumors. Dr. William Dove and his colleagues also have begun to focus on genetic factors that influence breast cancer development.