Despite advances in surgery and therapy, Glioblastoma (GBM) remains the most common and deadliest brain cancer in adults. Research shows that Glioblastoma tumor recurrence and therapeutic resistance has been attributed to Glioma-Initiating Cells (GICs) within the tumor that display several characteristics of neural stem cells.
“With a median patient survival rate between 10-15 months, identifying pathways critical for GIC function is essential for developing new strategies to target these cells and improve survival for Glioblastoma patients,” said Lawrence M. Pfeffer, PhD, professor in the Department of Pathology and director of the Center for Cancer Research at the University of Tennessee Health Science Center. He recently authored a paper published in the journal Oncotarget, entitled “The critical role that STAT3 plays in glioma-initiating cells: STAT3 addiction in glioma,” noting the critical role that proteins plan in Glioblastoma tumor growth.
In previous studies, Dr. Pfeffer’s lab reported that Signal Transducer and Activator of Transcription (STAT) proteins are involved in many cellular functions including activation in various cancers. STAT3 proteins in particular play a critical role in promoting GBM tumor growth and the growth of new blood vessels in the body, inhibit immune responses, and promotes tumor invasion and metastasis.
“In this study, we showed that regulation and/or deletion of this particular protein, STAT3, markedly inhibited tumor formation and growth in various pro-tumorigenic pathways,” Dr. Pfeffer said. “Moreover, we discovered that certain STAT3 modification sites are vital and fundamental for GIC formation.”
“To study this specific protein’s function, Dr. Pfeffer’s lab developed a system that can be manipulated to reduce STAT3 protein expression in Glioma-Initiating Cells. The goal is to determine in certain tumorigenic pathways whether non-modifiable amino acids introduced at specific STAT3 sites play distinct roles in Glioma-Initiating Cell function in vitro and in vivo.”
“Since STAT3 is an important driver in Glioblastoma tumor formation and development, the identification of these STAT3-regulated pathways in Glioma-Initiating Cells will inform the development of better targeted therapies against STAT3 in GBM and other cancers,” Dr. Pfeffer said.