HIV: Disease Becomes Ally in Fight Against Cancer
Study shows how a potent HIV gene could spur new cancer treatments
November 01, 1999
The enemy of my enemy is my friend - even if he was once my enemy. HIV, the virus responsible for the AIDS epidemic, uses a genetic arsenal that researchers at the University of Rochester Medical Center are turning against another enemy: cancer. If one particular HIV gene, called vpr, is tamed, it may open the door to a type of chemotherapy against which tumors cannot build a resistance. Patients with cancer today usually rely on chemotherapy but its effectiveness wanes if the tumor builds resistance.
"The hallmark of the AIDS virus is its ability to destroy immune cells," says Vicente Planelles, Ph.D., assistant professor of Medicine at the University of Rochester. "It sets vpr lose in the immune cell, and the cell just kills itself. We wanted to know what vpr is doing that makes it such a lethal instrument and how we could use it against cancer." Vpr killed every tumor Planelles tested it against.
Current chemotherapy methods rely on a protein called p53 that lives in most human cells. Like an emergency brake, this protein stops a cell dead in its tracks if it starts growing uncontrollably - a sign of cancer. Chemotherapy enhances the braking power of p53, but the longer a patient receives chemotherapy the more the runaway cells adapt to it and overpower the brake.
"Vpr uses a completely different method of arresting cells than p53 does," explains Planelles. Instead of stepping on the brakes like p53, it's as if vpr tears off the wheels. "We have not found a single human cancer that vpr did not kill. It seems to interrupt a fundamental life-process of a cell - something that the cell probably can't live without."
Doctors discovered vpr in 1983, but it wasn't until the mid-eighties that they realized its lethal nature. Planelles is now trying to tease out exactly how vpr kills so effectively. If he can figure out each step from vpr production to cell death, he may be able to find a way of engineering a vpr-like treatment that takes aim specifically at cancer cells. On the flip side, understanding just how vpr works means doctors might be able to blunt its harmful effects in HIV-positive people.
"What Planelles learns about the mechanism underlying vpr and how it causes arrest will teach us a lot about the cell cycle and how it can be manipulated therapeutically," adds Joseph D. Rosenblatt, M.D., chief of Hematology-Oncology at the University of Rochester and co-author of a recent study by Planelles that was published in Experimental Cell Research. "The role of vpr is not fully understood with respect to the AIDS virus. Vpr function should tell us a lot about t-cell depletion in AIDS patients."
Since vpr is a single gene of the many that make up the AIDS virus, it's impossible for someone to contract AIDS from the gene alone.
This study was funded entirely by the National Institutes of Health.