The worst form of brain cancer, glioblastoma multiforme (GBM), is considered largely incurable by doctors. Victims generally die within a year and a half of being diagnosed with the tumors. It’s such a devastating disease that the National Academy of Sciences calls it “the Terminator.” But an innovative nanotech-based “end-run” around cancer cells by Tel Aviv University researchers could provide doctors with a new way to treat – or even cure – GBM and other malignant killer cancers.
The technique, developed by Prof. Dan Peer of TAU’s Department of Department of Cell Research and Immunology and Scientific Director of TAU’s Center for NanoMedicine, has proven itself in the past: It’s based on the “cancer bullet” system Peer and other TAU researchers developed that delivers chemotherapy directly to cancer cells, using bioadhesive liposomes (BALs), consisting of regular liposomes reduced to nano-sized particles that attach themselves to the cancerous cells. Peer and Prof. Rimona Margalit, with whom he developed the method, have published several studies showing its effectiveness.
That research was done on ovarian cancer tumors, and it proved to be effective – but that wasn’t the case when it came to GBM, which is far less responsive to chemotherapy. Prof. Zvi R. Cohen, Director of the Neurosurgical Oncology Unit and Vice Chair at the Neurosurgical Department at Sheba Medical Center at Tel Hashomer Hospital in central Israel, contacted Peer to discuss whether anything could be done for individuals suffering from the aggressive and fatal form of brain cancer.
“I was approached by a neurosurgeon insistent on finding a solution, any solution, to a desperate situation,” said Peer. “Their patients were dying on them, fast, and they had virtually no weapons in their arsenal. Prof. Zvi Cohen heard about my earlier nanoscale research and suggested using it as a basis for a novel mechanism with which to treat gliomas,” the cancers that originate in glial cells in the spine or brain, of which GBM is the most devastating.
Cohen had acted as the primary investigator in several glioma clinical trials over the last decade, in which new treatments were delivered surgically into gliomas or into the surrounding tissues following tumor removal.
“Unfortunately, gene therapy, bacterial toxin therapy, and high-intensity focused ultrasound therapy had all failed as approaches to treat malignant brain tumors,” he said. “I realized that we must think differently. When I heard about Dan’s work in the field of nanomedicine and cancer, I knew I found an innovative approach combining nanotechnology and molecular biology to tackle brain cancer.”
With the same methods he and Margalit used to target ovarian cancer cells, Peer delivered RNA genetic interference (RNAi) material to human brain cancer cells transplanted into mice. The material was delivered directly to the tumor site using lipid-based nanoparticles coated with the polysugar hyaluronan (HA) that binds to a receptor expressed specifically on glioma cells, comparing the results with a control group that was treated with standard chemotherapy methods.
The results, said Peer, were “astonishing,” with the RNAi material hitting the cancer cells directly and extending the life of the test group versus the control group by a significant factor.
“Cancer cells, always dividing, are regulated by a specific protein,” said Peer. “We thought if we could silence this gene, they would die off. It is a basic, elegant mechanism and much less toxic than chemotherapy. This protein is not expressed in normal cells, so it only works where cells are highly proliferated.”
A hundred days following the treatment of four injections over 30 days, 60 percent of the afflicted mice were still alive. This represents a robust survival rate for mice, whose average life expectancy is only two years. The control mice died 30-34.5 days into treatment.
“This is a proof of concept study which can be translated into a novel clinical modality,” said Prof. Peer. “While it is in early stages, the data is so promising — it would be a crime not to pursue it.”