The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancers

PUBLIC ABSTRACT

There is accumulating evidence that inflammation of the prostate may contribute to prostate cancer. Studies implicate prostatic infections and sexually transmitted diseases with an increased risk of prostate cancer and the intake of antioxidants and anti-inflammatory drugs with a decreased risk. All of this data is consistent with the possibility of a novel infectious agent causing a chronic inflammation that leads ultimately to cancer. Recently, a novel virus, Xenotropic murine retrovirus (or XMRV) was discovered in prostate cancers of individuals with defects in RNase L function. Retroviruses have long been recognized to cause various human and animal cancers, and they are the primary focus of research in our laboratories. We propose that XMRV may be an initiating factor in human prostate cancer development. We will characterize this novel virus and explore its possible carcinogenic mechanisms through studies in cell culture, in a mouse model, and in human prostate cancer tissues.

Confirmation that prostate cancers are indeed caused by a new human retrovirus would have important and immediate implications for diagnosis and treatment. Clinical management of patients with a premalignant condition known as prostatic intraepithelial neoplasia or PIN is particularly difficult. It is impossible to tell from a biopsy with PIN if there is also frank cancer elsewhere in the gland. It is also currently not possible to predict how soon PIN will progress to cancer in a particular patient. Typically these patients are subjected to repeated biopsies. A second marker, such as the presence of XMRV, which predicts the potential for carcinogenesis and the likelihood of progression to cancer, would greatly simplify the diagnosis and management of prostate cancer. The experiments we propose will examine the possibility of XMRV being such a specific marker for predictor of serious disease. These studies could provide much needed help in developing a rational clinical approach to patients with high prostate specific antigen levels, presence of PIN, but no frank cancer. Such improved diagnostic tools could be applied rapidly after validation.

The confirmation that a novel human virus is a trigger or cause of prostate cancer would constitute a major conceptual change in our understanding of this cancer and could revolutionize treatment of disease. Such findings would quickly lead to the development of novel ways to treat prostate cancer by attacking the virus and the functions of its oncogenic proteins. The history of retroviral disease in humans would suggest that pharmacological inhibition of virus replication -- readily achieved for many years in HIV-1 infected individuals -- can dramatically limit the pathologic consequences of chronic viremia, and so could possibly prevent prostate cancer. These efforts could begin within months of the completion of this study, because good antiviral drugs are already in hand.