Protein Interaction May Provide Target for Brain Cancer Therapies

Discovery may provide hope for treatment of most common form of brain cancer.

Researchers have uncovered an interaction between proteins that may offer a target for the treatment of the most common form of brain cancer.

In a study recently published online in the journal Cancer Research, a novel interaction was found between the AEG-1 and Akt2 genes that regulate the malignant characteristics of glioblastoma multiforme (GBM). The AEG-1 gene was previously discovered to be overexpressed in the vast majority of cancers, while the Akt2 gene is overexpressed in several additional types of cancer.

The current study was able to demonstrate a positive feedback loop between the proteins expressed by the 2 genes that promote the growth and survival of GBM.

"This is the first time that this specific protein-protein signaling complex has been identified in GBM, and it gives us a new potential target for drug development," lead author Paul B. Fisher, MPh, PhD said in a press release. "If we can develop drugs that disrupt the interaction between these two proteins, we could potentially combine them with conventional therapies to more effectively treat malignant gliomas."

The researchers found interaction between the AEG-1 and Akt2 proteins to be crucial for further Akt2 signaling, which regulates tumor cell survival, proliferation, and invasion, the study noted. In an analysis of patient tissue samples, the results showed AEG-1 and Akt2 expression correlates with GBM progression and diminished patient survival.

The researchers were able to disrupt AEG-1 and Akt2 interaction through a process called competitive binding during preclinical experiments. The experiments revealed a decrease in GBM cell survival and invasion as a result of the competitive binding process.

A significant increase in survival was subsequently found after the process was combined with AEG-1 silencing in mouse models of human GBM.

"In this study we mapped the interacting regions in both genes in order to begin the process of developing drugs that can fill in these spaces and block the genes from binding," Dr. Fisher said. "If successful, these new treatments could also be applicable to a variety of additional cancers in which both genes are overexpressed."