More and more in recent years, cancer biologists are pointing their fingers at viruses. Human papillomavirus, they found, causes cervical cancer; hepatitis B induces liver cancer; and Epstein-Barr virus has been implicated in lymphoma. Most recently, scientists discovered that malignant brain tumors called glioblastoma multiforme, the late-stage version of the cancer that has afflicted Senator Edward Kennedy of Massachusetts, are almost always teeming with cytomegalovirus (CMV), a common, typically harmless herpesvirus. Although the nature of the association is still a mystery, researchers are already taking advantage of the link to find new cancer treatments.
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.
What was not obvious was why, exactly, the infection was there. Did CMV cause the cancer, or did it simply proliferate in tumor cells? “It’s a chicken-and-egg question: What came first, the virus or the tumor?” Mitchell points out. Glioblastoma patients have compromised immune systems, which might enable a latent CMV infection to reactivate, Mitchell says. And CMV might be frequently found in brain tumor cells because these cells are easy to infiltrate. A 2008 study Cobbs published in Nature revealed that a cell-surface receptor responsible for letting CMV inside is more frequently found on brain tumor cells than other cell types.
Cobbs, now at San Francisco’s California Pacific Medical Center Research Institute, 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. Still, no one has shown that CMV can turn healthy cells into cancer cells, Kalejta notes. So although the virus has some of the tools necessary to cause cancer, there is no proof that it does.
The good news is that when it comes to formulating cancer treatments, understanding the details of CMV’s link to brain cancer is less important than the link itself. “For our purposes, it doesn’t really matter,” says Mitchell, whose lab focuses on new cancer treatments. “We see the presence of the virus as a unique opportunity to go after it as a target in tumor cells.” His lab has “trained” immune system cells to recognize CMV proteins and has used those cells to identify and kill CMV-infected tumor cells.
Mitchell and his colleagues are currently testing their vaccine—and a second version using a different immune cell—in clinical trials, and although they have not yet published their results, he says that outcomes look promising. Cobbs, for one, is hopeful. “I’m holding my breath,” he remarks. “It looks like this may be a radically new way to consider treating these tumors.”
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4 Comments
Add CommentWhat a startling piece of valuable research. My late father's brain tumour was difficult to manage. I published a book about it - it was a difficult memoir to write. We had little information. How wonderful that such a disease may be preventable.
Reply | Report Abuse | Link to thisAs a clinical virologist I am very disappointed in your choice of title for this article. Clearly your choice of "Herpes" as the cause of Sen. Edward Kennedy's brain cancer was meant to grab attention when in reality the cytomegalovirus (CMV) is the true putative cause of these tumors. Shame on you for going for the misleading and attention grabing headline rather than the facts. The previous commenter is a perfect example of the misinformation this type of journalism perpetuates.
Reply | Report Abuse | Link to thisI could not find a way to contact the author, so decided to ask my question here. I wander if someone can answer the question here or/and in another article.
Reply | Report Abuse | Link to thisThis article describes a problem - 1. why do only a small number of people (with virus) develop brain tumors? 2. Why virus actively reproducing in these tumor cellsand not in healthy cells nearby?
It looks like the answer is (almost) given in this article http://www.scientificamerican.com/article.cfm?id=experts-gene-therapy i.e. virus may insert its DNA to a random place in human DNA. Sometimes that may change DNA code in a way causing cancer (answer to question 1). All tumor cells are descendants of this one unlucky cell and so they all have virus DNA in them (answer to question 2). If that is true (that I do not believe, because that is too simple to be true) other types of cancer may be caused by a virus too. If that is true, DNA of any tumor cell may be sequenced and compared to DNA of other cells of the same person to find out DNA sequence of that virus. The immune system of the person may then be taught to attack tumor cells in a way described in yet another ScientificAmerican article.
Of course real science is not done by people reading ScientificAmerican. I am just asking a question if the two articles describe facts correctly, why the above is not correct?
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