Engineered Drug May Directly Fight Glioblastoma Tumors

Berubicin, a new drug being developed for the treatment of glioblastoma, may be able to actually access and treat glioblastoma cells in the brain, according to the drug’s manufacturer.

The drug — which belongs to a class of powerful anthracyclines – is the first of its kind to cross the blood-brain barrier and attack brain tumors directly in clinical testing. In phase 1 clinical trials, 44 percent of patients showed significant anti-tumor activity, according to a CNS Pharmaceuticals press release.

Glioblastoma — a highly invasive brain tumor with limited response to current therapy – is the most common type of brain cancer with a very grim prognosis. With more than 12,000 cases projected in the US for 2018 alone, these patients only have a median survival of 14.6 months.

Most often, treatments such as surgery, chemotherapy, radiation, tumor treating fields (TTF) therapy or targeted therapy only slow progression of the disease and reduce symptoms.

These tumors are typically unresponsive to therapy because of the blood-brain barrier, which is made up of special endothelial cells that restrict the passage of substances from the bloodstream to the brain. Ultimately, this keeps any disease-causing pathogens from entering the brain, but in glioblastoma cases, it also keeps effective treatment regimens out.

“Glioblastoma is the most aggressive form of brain tumors that usually kill most of the people that are diagnosed with it,” Sandra Silberman, M.D., Ph.D., Chief Medical Officer at CNS Pharmaceuticals, said in an interview with CURE. “The reason is because of the blood-brain barrier; it keeps out any poisons or toxins that are floating around in your bloodstream because your brain is one of the most important organs in the body.”

“There are things that get across: notably, the things that cause neurological changes, cannabis, carbon monoxide,” she added. “But some of the bigger molecules just don’t, and there is no way to get the most potent drugs we have for glioblastoma in to the brain.”

Since anthracyclines are considered highly potent anticancer drugs, Berubicin has the potential to effectively treat glioblastoma so long as it can breach the blood-brain barrier. Preclinical studies showed that the agent was a “destructive drug that looked very active for glioblastoma and a number of different glioblastoma cell lines that survive from original glioblastomas,” said Silberman.

“Anthracyclines are one of the most potent drugs we have as hematologists and oncologists for multiple diseases. It has been a mainstay for leukemia for many years,” she added.

Waldemar Priebe, Ph.D., professor of medicinal chemistry at the Department of Experimental Therapeutics at the University of Texas MD Anderson Cancer Center, changed anthracycline to help treat glioblastoma. “He has done it in a number of ways, many of which he has used before in modifying these types of molecules so that they are either more potent or they overcome resistance and then in this case, it overcomes the blood-brain barrier so it gets in to the brain,” Silberman explained.

Since, CNS Pharmaceuticals has acquired the licensing for Berubicin and hopes to initiate a phase 2 trials to evaluate its safety and efficacy in a larger population of patients.

“Until we find something that is one-size-fits-most we are stuck with chemotherapy, radiation therapy and surgical techniques to deal with the tumor,” Silberman said. “Berubicin would add another dimension of treating the tumor: If it shrinks the tumor, it could limit the amount of surgery that needs to be done; or after failure to prior drugs, seeing if this new drug can overcome resistance the tumor has shown to prior drugs and therapies and actually prolong the life of the patient.”

“The impact that this drug could have on patients could be exceptional,” she added.