Cancer cells are sick, but they keep growing because they don't react to internal signals urging them to die. Now researchers at Washington University School of Medicine in St. Louis have found an efficient way to get a messenger into cancer cells that forces them to respond to death signals. And they did it using one of the most sinister pathogens around - HIV.
"HIV knows how to insert itself into many different types of cells," says senior author William G. Hawkins, M.D., assistant professor of surgery and a member of the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital. "A portion of the HIV protein called TAT can transport biologically active compounds into cells. TAT is small, but it can move massive molecules. You could almost hook TAT up to a train, and TAT would drag it inside a cell. So we've taken advantage of this ability."
In an article published online in January 2007 in the Annals of Surgical Oncology, the researchers describe using TAT to pull a protein called Bim into cancer cells. TAT alone cannot cause AIDS and has no adverse health effects. Bim acts as a tumor suppressor and causes cancer cells to die through apoptosis, a process by which cells "commit suicide."
The research team found that the TAT-Bim compound activated apoptosis mechanisms in cancer cells and augmented the cell-killing effect of radiation. When mice with malignant tumors were treated with TAT-Bim, their tumors shrank, and they survived longer than mice that didn't get the treatment. After 40 days, 80 percent of mice receiving TAT-Bim were alive compared to 20 percent of mice that didn't get the treatment.
Hawkins asserts that this success marks the beginning of a very promising new approach to cancer therapy. "This is the tip of the iceberg," he says. "Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die."
Hawkins says he thinks treatments that activate apoptosis mechanisms could provide new options for patients with the deadliest cancers - such as pancreatic cancer - which have very low rates of survival. He says he believes that clinical trials of these compounds could be just a few years away.