New implant with three drugs doubles survival in brain cancer mice

Researchers at the University of Cincinnati and Johns Hopkins Medicine created a new way to fight glioblastoma, a deadly brain cancer. They embedded three drugs into a mesh made of electrospun nanofibers—extremely thin strands of material created using an electric field. The implant delivers medication directly to the tumor site after surgery.

Glioblastoma is the most common and aggressive form of brain cancer in adults. The three drugs used—temozolomide, acriflavine, and PT2385—are already approved by federal regulators. But when combined, they work far better than any single drug alone. "When you add them together, three things can happen," said Andrew Steckl, a distinguished research professor at UC. "The combination is negative; the effect is additive, like one plus one equals two; or it's synergistic, which is like one plus one equals three."

Brain cancer is notoriously hard to treat for several reasons. Cancer cells mutate quickly to escape treatment. Tumors also tend to come back even after initial therapy. Additionally, the blood-brain barrier—which normally protects the brain from toxins—also blocks many traditional cancer drugs from reaching tumors. "It comes in through the window and when you close the window, it comes through the door," Steckl said, describing how the cancer adapts.

The nanofiber mesh solves these problems by placing multiple drugs directly at the tumor site. This approach lets doctors control exactly how much medicine is released and for how long. The implant also protects the rest of the body from toxic side effects because the blood-brain barrier keeps the drugs localized to the brain. "Our NanoMesh system was designed to solve these issues by enabling localized long-term delivery of multiple synergistic drugs directly at the tumor site after surgery," said Daewoo Han, an assistant professor in UC's College of Engineering and Applied Science and lead author of the study, published in ACS Biomaterials Science & Engineering.

Animal trials showed dramatic results. Untreated mice with glioblastoma died within 19 days. Most mice receiving the three-drug nanofiber implant survived about twice as long. Even more striking, 40 percent of treated mice survived past day 120—the end of the experiment—with survival leveling off for more than 80 days. "In our study, a three-drug combination showed strong synergistic effects across multiple glioblastoma models and significantly improved survival in animal studies," Han said.

Betty Tyler, a professor of neurosurgery at Johns Hopkins Medicine who worked on the research, stressed the need for multiple approaches. "Unfortunately, cancers know how to pivot to evade therapeutic treatment," Tyler said. "So we're approaching treatment multidimensionally." She noted that existing therapies have helped patients live longer. "Current therapies have increased patient survival and given them more birthdays," Tyler said. "But we're still working on improving options."

The research team is now refining the technology to improve long-term drug release. Han said the system has potential for treating many difficult cancers beyond glioblastoma. "Our ultimate goal is moving forward to a clinically translatable system that improves both survival and quality of life for patients with difficult-to-treat cancers, including glioblastoma," Han said. "What's next will be very exciting."