Baltimore, MD July 19, 2011. Researchers at the University of Maryland School of Medicine have discovered a novel interaction between two proteins involved in regulating cell growth that could provide possible new drug targets for treating diffuse large B-cell lymphoma, the most common type of non-Hodgkin's lymphoma.
In a study published online in Nature Communications, the scientists report that they have found a complex molecular and functional relationship between ERK (extracellular signal-regulated kinase), a protein that helps to regulate cell proliferation and survival, and CHK2 (checkpoint kinase 2), a protein that is involved in the cellular DNA damage response. They also demonstrated, for the first time, elevated levels of both proteins in diffuse large B-cell lymphoma cells, compared to non-cancerous cells.
Ronald B. Gartenhaus, M.D., associate professor of medicine at the University of Maryland School of Medicine and the senior author, says researchers found that CHK2 appears to regulate the activity of ERK, although the exact mechanism is not clear. "The two proteins physically interact, which was not known before, and we may be able to use this interaction for therapeutic advantage. We found that treating human B-cell lymphoma cells with both an ERK inhibitor inhibitor and a CHK2 inhibitor killed substantially more cancer cells than treating the cells with either drug alone," he says.
"Based on our findings, we believe that a combination therapy targeting both ERK and CHK2 could offer a potential new approach to treating diffuse large B-cell lymphoma," says Dr. Gartenhaus, who is co-leader of the Program in Molecular and Structural Biology at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.
The drugs used to inhibit ERK and CHK2 caused the cancer cells to die through a process called apoptosis, or programmed cell death. Human cells normally self-destruct in a controlled manner, but
|Contact: Karen E. Warmkessel|
University of Maryland Medical Center