Journal Publishes Paper on UTHSC Research that May Lead to Breakthrough in Treating Most Deadly Form of Brain Cancer

Memphis, Tenn. (Aug. 9, 2013) – Despite the advances in cancer treatment during the last few decades, there has been little improvement in the care of patients with the deadliest form of brain cancer, glioblastoma. The median survival rate for patients with this aggressive form of brain cancer, which took the life of U.S. Sen. Edward M. Kennedy, college basketball coach Jim Valvano and baseball player Gary Carter, has remained at less than one year for several decades.

Research done at the UTHSC Center for Cancer Research (CCR) to better understand these highly malignant tumors may be a major step in one day providing better treatment options. The research is detailed in a paper accepted for publication in The Journal of Biological Chemistry.

CCR Director and Interim Vice Chancellor for Research Lawrence M. Pfeffer, PhD, along with graduate student and PhD candidate Jo Meagan Garner and others in collaboration with researchers from St. Jude Children’s Research Hospital identified signaling pathways in the subpopulation of cancer stem cells in glioblastomas that allow for their aggressive growth and resistance to most forms of therapy. “We show that you can use inhibitors to block this pathway and affect the properties of the cancer stem cells selectively,” Dr. Pfeffer said.

The paper, titled “Constitutive activation of STAT3 and NF-kB signaling in glioblastoma cancer stem cells regulates the notch pathway,” is currently published in the online version of the journal and will be in print in October.

“The idea is to identify the properties of these glioma cancer stem cells, because the problem is that we’re good at curing cancer in the test tube and in some model systems, but the reality is, in patients, we don’t do very well,” Dr. Pfeffer said. “The problem is that there is a small subpopulation of cancer stem cells in gliomas that are primordial-like cells, which are highly resistant to most forms of therapy. If we can better characterize these cells, we could better target this subpopulation of cancer stem cells, which is resistant to chemotherapy and usually repopulates the tumor after therapy.”

Dr. Pfeffer, the Muirhead Professor and vice chair of the Department of Pathology, said the research, done in vitro and in vivo, took several years to bring to fruition. “We showed that these stem cells are tumor initiating cells, so when you put them into mice, they form tumors at a much greater capacity than the original glioma line that we started with,” he said.

The studies were done in collaboration with St. Jude researcher, Andrew Davidoff, MD. “This illustrates the excellent working relationship between UTHSC and St. Jude,” Dr. Pfeffer said.

“We have identified a signaling pathway that we could possibly target to try to treat gliomas, and we’re going to try that in the future,” he said.

“First of all, we could test for this pathway being activated in patients, so we can identify them, and maybe design strategies in personalized medicine to target them specifically, and that’s the goal of this project.”

The research is potentially important on a clinical level and “may be a major step in providing a treatment option for a subgroup of patients with glioma,” Dr. Pfeffer said.