Cancer researchers, led by Antonio Giordano, MD, PhD, associate professor at Jefferson Medical College, have for the first time found direct evidence of a potential role for a monkey virus in the development of mesothelioma.
In research reported in the August 3 issue of Nature Medicine, Dr. Giordanos team found that simian virus 40 (SV40), a DNA tumor virus from monkeys, targets key proteins that normally prevent tumors from forming, rendering them ineffective. These proteins, made by tumor-suppressor genes, are in the retinoblastoma family (pRb, pRb2/p130, and p107). SV40 T-ag binds to and inactivates the tumor-halting proteins. The discovery underscores the important role that Rb family proteins play in controlling cell growth.
We are not saying that the virus is the only factor; clearly there is more than one factor involved in the onset of mesothelioma, said Dr. Giordano. It is a complex mechanism.
According to Dr. Giordano, the finding could have important implications for developing cancer diagnostics, even a potential test for the early development of cancer. There are implications that the pRb2/p130 gene could also be involved in the development of other cancers, such as ovarian and breast.
Previous studies by other researchers had shown the presence of SV40 in animals and in some cases in humans. No one knew whether the virus played a direct role in causing disease, however. The discovery by Giordano's team of a potential mechanism for some cases of disease development strengthens the possible contributory role for the virus.
Although mesothelioma is one of the most aggressive human cancers, no one had reported alterations of important cell cycle controllers, such as Rb family genes, said Dr. Giordano. When we studied Rb family genes in mesothelioma, we were surprised to find that the genes were present in normal levels. This led us to study why the genes are present, but not working.
Armed with new information about SV40s interaction with Rb family proteins, Dr. Giordanos team is pursuing research that may lead to new treatments for mesothelioma and lung cancer. The team hopes to identify the source of SV40 infections in humans and understand how the virus is transmitted. They are also working to develop a gene therapy approach to restore growth-suppressor function of the pRb2/p130 gene. To date, the treatment has shown success in animal studies and is about to enter phase 1 clinical trials in humans.