In the search for the cause of cancer, viruses were early suspects, but by and large were acquitted of responsibility. Now scientists, aided by a more sophisticated understanding of cancer and armed with more sensitive techniques are reopening the investigation. The latest front is the discovery that glioblastoma, the form of aggressive brain cancer afflicting Senator Ted Kennedy, may be caused by a common virus, cytomegalovirus (CMV). This raises the tantalizing possibility that glioblastoma, notoriously difficult to control with chemotherapy or radiation, might be treated or prevented with a vaccine.
Several forms of cancer have been known to be associated with common viruses. Burkitt’s lymphoma, a fast growing cancer that is rare in the US, but common in Africa is known to be associated with Epstein-Barr virus, the same virus that causes mononucleosis. Liver cancer is known to be associated with hepatitis B and hepatitis C viruses. The association of these viruses with cancer does not necessarily mean that the viruses cause the cancer. It is possible that the virus interferes with the normal immune response, rendering the infected person more likely to develop cancer, or less likely to be able to attack cancer that develops spontaneously in the affected organ.
The first cancer shown to be definitively caused by a virus is cervical cancer. It now appears that virtually all cases of cervical cancer are caused by human papilloma virus (HPV) a common, sexually transmitted virus. Scientists have been able to replicate the malignant changes in HPV cervical cells in the lab, demonstrating cause and effect. That has lead in turn to the development of a vaccine against HPV that should prevent or dramatically reduce the incidence of cervical cancer.
The association between CMV and brain cancer, like many great medical breakthroughs, was discovered by accident. According to Virus in the Brain, in the January 2009 issue of Scientific American Mind:
The saga began in the late 1990s, when Charles Cobbs, a neurosurgeon then at the University of California, San Francisco, started pondering the link between inflammation and brain cancer. Malignant tumors are often associated with abnormal immune activity, and he wanted to know why. “Is it just something that happens out of the blue, or is it possible that there’s something maybe driving that inflammatory cascade?” he recalls wondering.
Because they elicit immune responses, infections immediately sprang to mind as possible candidates. Cobbs and his colleagues analyzed glioblastoma samples from 22 patients and found that all harbored CMV. Four out of five people have this virus, which remains in the body for life. Usually a person’s immune system keeps CMV in a latent state in which it does not replicate, but Cobbs found the virus actively reproducing in these tumor cells and not in healthy cells nearby. “It was stunningly obvious that these tumors were infected,” says Cobbs, whose findings, published in Cancer Research in 2002, were confirmed in 2007 by Duke University neuro-oncologist Duane Mitchell.
Does CMV cause brain cancer?
Cobbs … believes that CMV plays a more active role in generating tumors. He points to a study published in May in Science showing that CMV makes proteins that “turn off” human genes important for preventing unwanted cell growth, a prerequisite to tumor development. It is as if CMV is “clipping the brake line,” remarks study co-author Robert Kalejta, a molecular virologist at the University of Wisconsin–Madison. Other studies have shown that CMV can interrupt a cell’s ability to commit suicide when the cell growth has gone awry…
These observations do not prove that CMV causes brain cancer. Only lab experiments that show CMV cells becoming cancerous could prove a causal relationship. However, the close association and ability of CMV to turn of the mechanism that usually prevents cancer from developing within a cell means that treating the CMV infection might treat brain cancer or even prevent it.
Cobbs has shown that immune cells sensitized to proteins produced by the CMV virus can identify and destroy CMV infected brain cancer cells. A Swedish group has been investigating the use of anti-viral medications to prevent recurrence of brain cancer treated with chemo or radiation. Perhaps most exciting is ongoing development of a CMV vaccine with the aim of preventing brain cancer. Although the work is still in the earliest stages, the first small trial has shown that the CMV vaccine extends the average survival time for glioblastoma patients from 15 to 20 months. These methods, alone or in combination, may radically change the way that we treat brain cancer and even allow us to prevent it.
The discovery of the association of CMV with brain cancer raises the number of virus associated cancers to four, and suggests that a search for viruses in tumors, using new and more sophisticated tools, may yield new and surprising associations, and open up exciting avenues for treatment and prevention of other types of cancer.