HIV Protein Recruited To Kill Cancer Cells

Now, researchers have found an effective way to get a messenger into cancer cells that forces them to respond to death signals. They accomplished this by using one of the most vicious pathogens that exist--HIV.

In an article published online in January 2007 in the Annals of Surgical Oncology, researchers from the Washington University School of Medicine in St. Louis (MO, USA) described using a protein known as Tat (transactivator protein) to pull another protein called Bim into cancer cells. Tat alone cannot cause AIDS and has no undesirable health effects. Bim acts as a tumor-suppressor and causes cancer cells to die through apoptosis, a process by which cells commit suicide.

"HIV knows how to insert itself into many different types of cells,” stated 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 (St. Louis, MO, USA). "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.”

The research team discovered 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 did not receive the treatment. After 40 days, 80% of mice receiving Tat-Bim were alive, compared to 20% of mice that did not get the treatment.

Dr. Hawkins asserted that this achievement marks the beginning of a very promising new approach to cancer therapy. "This is the tip of the iceberg,” he stated. "Now that we've proven we can do this, we've started creating a battery of proteins that can push cancer cells to die.”

Dr. Hawkins believes treatments that activate apoptosis processes could provide new options for patients with the deadliest cancers--such as pancreatic cancer--which have very low rates of survival. He thinks that clinical trials of these compounds could be just a few years away.

Dr. Hawkins began evaluating Tat-Bim after discussions with co-author Richard S. Hotchkiss, M.D., professor of anesthesiology, medicine, and surgery, and associate professor of molecular biology and pharmacology. Dr. Hotchkiss was looking for proteins that suppress apoptosis in patients with life-threatening infections and discovered that Tat-Bim had the unwanted effect of increasing cell death. Dr. Hawkins wondered if Tat-Bim could be effective against cancer, and a collaboration began between their labs to utilize the anticancer potential of Tat-Bim.

"Unlike most healthy cells, cancer cells grow very fast. So they are always on the verge of running out of natural ingredients like sugars, and mistakes are accumulating in their DNA,” Dr. Hawkins remarked. "This results in signals telling cancer cells to die, but the cells don't quite have the permission they need to do it. Proteins like Tat-Bim can tip the balance in favor of death.”

To additionally augment the cancer-killing power of Tat-Bim and similar proteins under development, Dr. Hawkins and his colleagues are now working on a technique that will concentrate them within tumors while sparing healthy cells. In collaboration with Robert H. Mach, Ph.D., professor of radiology, they are binding the anticancer proteins to tracer molecules that selectively bind to cancer cells. "Dr. Mach designed tracers to visualize cancer in PET [positron emission tomography] scans,” Dr. Hawkins said. "By binding our molecules to the tracers, we can deliver them to cancer cells. We've seen phenomenal results in the lab.”

In the next phase of research, Dr. Hawkins plans to combine pro-apoptotic proteins such as Tat-Bim with chemotherapy, radiation therapy, and other anticancer therapeutics in hopes of further increasing cell-suicide signals within cancer cells.


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Washington University School of Medicine