"Designer Protein" Opens the Door in Brain Tumor Research
Findings from Wake Forest Baptist Medical Center’s Brain Tumor Center of Excellence are redefining future treatments for brain cancer. Proteins designed by Waldemar Debinski, MD, PhD, director of the Brain Tumor Center of Excellence and professor of neurosurgery at Wake Forest Baptist, and colleagues provide a new way to target and destroy glioblastoma multiforme (GBM) cells, the most deadly form of brain cancer, without harming healthy cells.
Nearly two decades ago, Debinski and colleagues developed what Debinski has dubbed a “designer protein,” a single-chain protein that is able to seek out and make its way into specific cells, such as cancer cells. The challenge, and most recent focus of the researchers’ work, has been finding a way to program that protein, once inside the targeted cell, to locate and accumulate at a specific subcellular compartment such as the nucleus, which houses a cell’s DNA or the mitochondria without harming normal neighboring tissue.
With funding from the National Cancer Institute, Debinski and his colleagues have now accomplished just that—they have created a designer protein that not only targets a specific cell type, but then invades that cell and is drawn directly to a chosen compartment.
“Some radiation, if applied to the body, will do nothing to the cancer cells because it can’t penetrate far enough into the body to reach its specific site of action in the cells,” Debinski said. “However, if we deliver that same radiation directly to the nuclei of GBM cells, it can destroy the DNA of the cancer cell, leaving the cell unable to live any longer. It dies and the neighboring healthy cells go untouched. In this way, we think we may be able to provide a therapy that is both effective and at the same time less toxic.”
This research is the first to document in a direct way both a single-chain protein that can recognize GBM cancer cells and its journey from attaching to the cells’ surface to reaching the cells’ nuclei. While the use of a designer protein to deliver therapies to specific action sites must still go through extensive safety and animal research before it can translate to human patients, the current findings open the door to potential new treatments for this very hard-to-manage brain cancer.
“As a researcher, one can think and dream about many possible scenarios during the quest to find a way to treat cancer,” Debinski said. “This is one that we now know we can actually do. It’s feasible—and it’s fantastic. That’s the best way to describe it.”