VCU Researchers Make Major Advancements in Glioblastoma Research

According to EurekAlert!, a study at Virginia Commonwealth University has potentially pinpointed the so called “Achilles heal” of a certain type of deadly brain cancer: glioblastoma multiforme.

Glioblastoma, or glioblastoma multiforme, is a rare type of brain cancer that forms from cells called astrocytes. These star-shaped cells are the ones that support support nerve cells. Glioblastomas grow incredibly quickly, and are responsible for 20% of diagnosed brain cancers, affecting men more than women. Some symptoms of glioblastoma include persistent headaches, seizures, vomiting, trouble thinking or speaking, and changes in mood. There are various forms of treatment for glioblastoma including surgery, though glioblastoma typically does recur after initial treatment. To learn more about this cancer, click here.

To better understand this scientific research from VCU, it’s important to know what autophagy is. This is a cellular process where cells cleanse the body of unnecessary cells or components. Autophagy has the potential to be toxic or protective. Scientists at VCU discovered that autophagy plays a protective role in allowing glioma stem cells to fight off anoikis, a form of programmed cell death.

The research showed that the protective role is controlled by a gene called MDA-9/Syntenin.

“We discovered that when we blocked the expression of MDA-9/Syntenin, glioma stem cells lose their ability to induce protective autophagy and succumb to anoikis, resulting in cancer cell death,” said Paul Fisher, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine.

It was Dr. Fisher himself who first found the MDA-9/Syntenin gene. After his initial discovery, he along with others found the gene over-expressed in many cancers.

This finding will be crucial to continued cancer research and new treatments on the horizon. Tackling this “Achilles heel” of glioblastoma and other cancers could be the next step to finding a possible cure.

Fisher and his colleagues additionally noted that MDA-9/Syntenin sustains protective autophagy through activating BCL2, which is another gene that controls cell death. As for the toxic aspect of autophagy, MDA-9/Syntenin was also found to suppress high levels of this by epidermal growth factor receptor (EGFR) signaling. This means that not only does the gene protect cancer cells from dying, but it also suppresses the type of autophagy that would kill the cancer cells.

In scientific terms: “In the absence of MDA-9/Syntenin, EGFR can no longer maintain protective autophagy. Instead, highly elevated and sustained levels of toxic autophagy ensue that dramatically reduce cancer cell survival,” said Fisher.

The most incredible thing about this study is that it is the first of its kind. Never before has a study shown this type of connection between a single gene in the body and cancer cells.

Fisher expands on this thought: “This is the first study to define a direct link between MDA-9/Syntenin, protective autophagy and anoikis resistance. We’re hopeful we can exploit this process to develop new and more effective treatments for GBM and possibly other cancers,” he said.

Fisher and his team have not only done more research on this with patients who had undergone surgical removal of tumors, but also with mouse models. In both of these, MDA-9/Syntenin inhibition increased survival and outcome.

As for the future, Fisher’s team hopes to expand this research to other types of cancer, not just glioblastoma. Fisher is also trying to find new strategies to inhibit MDA-9/Syntenin expression. Regardless of these future projects, the current discovery alone is enough to boost cancer research and potentially offer more solutions to those with glioblastoma for now.

To read more about this incredible discovery, click here.