A research team at the University of Georgia’s Regenerative Bioscience Center has identified that a compound molecule used for drug delivery of insulin could be used for treating glioblastoma, an aggressive, usually fatal form of brain cancer.
Glioblastoma commonly called GBM, is a fast-growing, web-like tumor that arises from supportive tissue around the brain and resists surgical treatment. GBM cells have been described by some as “sand in grass,” because they are hard to remove and tend to reach out in a tentacle-like fashion to surrounding healthy brain tissue.
The National Foundation for Cancer Research reveals that more than half of newly diagnosed GBM patients die within the first 15 months. Late U.S. Sens. John McCain and Ted Kennedy both passed away from GBM, raising national awareness of the deadly disease.
Surfen is a pharmaceutical compound molecule first described in 1938 and is used to optimize insulin delivery. The UGA researchers found that surfen-treated cells were “blocked” from tumor growth, and the spread of tumor cells in the brain.
Lohitash Karumbaiah, associate professor of regenerative medicine in UGA’s College of Agricultural and Environmental Sciences, said, “This study shows that we can stifle the growth of invasive brain tumors with a compound that has a substantial clinical advantage, and can aid in the reduction or refinement of mainstream treatments, particularly radiation and/or chemo”.
The study is the first to use surfen as an application to treat GBM and has been published ahead of print in the FASEB Journal. To test their method, the research team started with cultured cells to observe the binding properties of the surfen compound. After this, they introduced live rodent models with cells that could grow into invasive tumors. The researchers observed that surfen-treated animals demonstrated smaller tumors and significantly reduced brain hemorrhage volume than control animals.
Meghan Logun, a graduate student working with Karumbaiah, said, “In basic terms, surfen is highly positively charged and will bind to negatively charged things. Since we study sugars in the brain, which are highly negatively charged, we then asked, ‘Why not try using positive charges to block off the negative ones?’”
Logun is now studying how brain cancer uses the highly charged elements in brain tissue to aid in invasion. She said, “In the surfen-treated animals, we saw that the tumors were actually much more constrained and had more defined boundaries”.
To study the surfen molecule in more detail, the team collaborated with Leidong Mao, associate professor in UGA’s College of Engineering and co-developer of a microfluidic device used to observe glycosaminoglycans (GAGs), the highly negatively charged molecules produced by brain tumors. The device is designed to mimic the neural pathways of the brain and thus allows for real-time monitoring of tumor cell adhesion and growth.
Mao said, “We did not expect to see such a robust response. Blocking off the charged GAGs from the tumor cells really did dampen their ability to invade.”
Based on this study’s findings that surfen had isolated the tumor, the team also analyzed MRI images to measure the treatment’s effectiveness.
Qun Zhao, associate professor of physics in the UGA Franklin College of Arts and Sciences and another RBC collaborator on the project, said, “In the MRI image you can see [the effects of the surfen treatment] pretty drastically, not in terms of killing the GBM but in blocking its prey,” “In the non-treated image, you see rampant invasive growth, compared to the surfen-models where you see a nicely contained and almost circular-shaped tumor.”
Karumbaiah said, “The tumor may still grow, but at least now it doesn’t have any invasive inroads to creep into other parts of the brain. That could be clinically beneficial for a surgeon wanting to remove the tumor and not having to worry about rogue cancer cells.”
Looking ahead, Karumbaiah is optimistic that repurposing a compound recognized as safe and with proven beneficial binding properties, could accelerate review and approval of this potential new therapeutic, and advance deliberation in helping to expedite the drug approval process.
Karumbaiah said, “Our hope is that, in the wake of this discovery, lives can be saved, and we can finally change the scope of this life-threatening disease. In my five years at UGA, this is the highest profile cancer paper I’ve ever had.”