The brain cancer glioblastoma is notoriously difficult to treat, largely because the blood-brain barrier prevents many drugs from breaking through and reaching their target. Now researchers in the U.K. say they’ve found a drug that can penetrate that barrier and invade glioblastoma tumors—AstraZeneca’s PARP inhibitor Lynparza (olaparib), which is FDA-approved to treat some patients with ovarian cancer.
In a study led by the University of Glasgow, 35 glioblastoma patients were given Lynparza with the chemotherapy drug temozolomide. The researchers then examined tumor samples and discovered that Lynparza burrowed into the core of the glioblastoma tumors in 27 of the patients, and in 10 of those people, the drug also reached cancer cells in surrounding areas that can be difficult to remove with surgery. The results were presented today at the National Cancer Research Institute’s Cancer Conference in Liverpool.
The patients in the trial had all relapsed after undergoing traditional treatments for glioblastoma. During the trial, they were given Lynparza intermittently, which helped minimize the risk of myelosuppression—reduced blood counts that can be a dangerous side effect of cancer treatments.
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Glioblastoma is the most common type of malignant brain tumor, representing 14.9% of all diagnoses, according to the American Brain Tumor association. The five-year survival rate for adults varies by age but is generally under 17%, says the American Cancer Society.
“While overall survival for cancer is improving, survival for brain [tumors] is still very low and the blood brain barrier is a significant pharmacological obstacle,” said Nigel Blackburn, Cancer Research U.K.’s director of drug development, in a press release.
Research groups around the world are experimenting with different methods for getting around the blood-brain barrier in treating glioblastoma. One potential method for doing that could involve immunotherapy treatments, which boost the ability of the immune system to recognize and attack tumors. A team of researchers at Duke University is testing a modified form poliovirus, for example. And in September, scientists at Washington University School of Medicine in St. Louis and the University of California at San Diego published research showing that in animal models of aggressive glioma, the Zika virus slowed tumor growth.
AZ’s Lynparza works by inhibiting PARP, an enzyme that normally allows cancer cells to repair their own DNA and continue multiplying. In October, the FDA granted priority review to the company’s application to expand the label of drug for use in some patients with aggressive breast cancer. The company recently released data from a clinical trial showing impressive results for Lynparza in patients with BRCA1 or BRCA2 mutations.
Due to the positive results from their initial glioblastoma trial, the U.K. research team is now planning two additional trials of the Lynparza-chemo combo. Those trials will recruit newly diagnosed glioblastoma patients and will test the drug cocktail along with radiotherapy.