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From the thrill of discovery to clinical application; Upstate researchers’ efforts to understand protein’s function could help target difficult-to-treat brain tumors

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From the thrill of discovery to clinical application; Upstate researchers’ efforts to understand protein’s function could help target difficult-to-treat brain tumors

Glioblastoma (GBM) is one of the most complex, deadly, and treatment-resistant cancers. According to the National Brain Tumor Society, over 14,000 people in the US will be diagnosed every year, and another 10,000 people will die from GBM. While survival and mortality rates remain unchanged for decades, Upstate researchers are embarking on a project to find an effective way to target and treat these brain tumors. Mariano Viapiano, PhD, and his lab will be using just under $500k over the next two years from the National Institute of Neurological Disorders and Stroke to learn more about a protein found in tumors’ cells. If successful, this approach could lead to more effective treatments for GBM, offering hope for better outcomes for patients with this tough-to-treat cancer. 

Dr. Viapiano and six members of his lab standing in his laboratory

Lab director and principal investigator Mariano Viapiano, PhD, second from right, with the team of the Upstate Brain Tumor Laboratory and Biorepository in 2021. From left, Leah Longo, research aide; Joan Chou, medical student; Sharon Longo, laboratory manager; John Longo, research specialist; Somanath Kundu, postdoctoral scientist; and Roshini Arivazhagan, postdoctoral scientist.

Viapiano’s brain tumor lab is focused on gliomas; tumors that form in the brain that are difficult to treat with chemotherapy and radiation.

“If we understand the mechanism that makes the cells resistant, we can develop the drug or an antibody or something to treat them,” says Viapiano. The problem? Not all tumors are the same.

“Within the tumor population, some cells have different mutations and mechanisms,” Viapiano explains. “You try to target one mechanism at a time and it's always an arms race against the tumor as a whole.”

To try and tackle this, Viapiano is looking at the cells "one level up" and found a mechanism common to all brain tumor cells.

“This is a very ingenious concept that a senior postdoc in my lab, Somanath Kundu, had a few years ago; there are different mechanisms that make these tumor cells resistant to therapy, so there must be some high-controlling mechanisms common to all of them. He started looking at this population of control proteins that are inside the tumor cells, and he identified a particular protein that belongs to a rare family.”

These proteins, called scaffolding proteins, help control how parts of the cell are organized. The lab's goal is to affect these “high-level targets” so that they can disrupt multiple cell functions all at once.

"They will have no way to escape therapy because now everything is disrupted. It's like messing with the central processing unit of the cells,” says Viapiano.

For the first part of the project, Viapiano’s lab will be working to understand more about how exactly these cell scaffolding proteins work within the tumor cells. Next, they will be trying to target them by creating a peptide that will fit within these proteins and disrupt them. Viapiano explains why these peptides may be the perfect solution.

"It’s so difficult to inject anything into your body’s circulation and make it go to the brain, but these peptides do. They have been used to treat stroke and we hope this will be the first time they are used to treat cancer.” If this strategy works, it may even have applications beyond glioblastoma. Scaffolding proteins can be found in other solid tumors, like prostate and breast cancer.

Translating his science from the laboratory to potential clinical use is a big motivator for Viapiano.

“One great resource that we have here at SUNY is the fact that I am faculty in both basic science and the neurosurgery clinical department, and that gives us access to a unique clinical component of research,” Viapiano explains. “We can obtain clinical specimens directly from the operating room and immediately start using them in the lab.”

“What motivated me throughout my career has been the thrill of discovery,” he continues. "The idea that we are doing research is very enticing to us from a basic science perspective, but I can envision bringing it to the clinical side. It might not happen tomorrow, and it might not even happen in our hands; but I always think if we at least get as close as we can it might inspire other people to say, ‘Oh, I'll take it from here.’”

You can read more about Viapiano's lab's work here.

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