Anti-psychotic drugs approved by the U.S. Food and Drug Administration (FDA) may possess potent tumor-killing activity against glioblastoma, says researchers from the University of California, San Diego School of Medicine.
Glioblastoma is the most common as well as the most aggressive malignant primary brain tumor worldwide. The tumor accounts for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors around the world.
Clark Chen, vice chairman of division of neurosurgery in UC San Diego, led the team of scientists and used shRNA technology platform to find out how genes in the human genome contrinuted towards glioblastoma growth. Chen said, “ShRNAs are invaluable tools in the study of what genes do. They function like molecular erasers. We can design these ‘erasers’ against every gene in the human genome. These shRNAs can then be packaged into viruses and introduced into cancer cells. If a gene is required for glioblastoma growth and the shRNA erases the function of that gene, then the cancer cell will either stop growing or die.”
The scientists found out that many of the genes necessary for glioblastoma growth were also required for dopamine receptor function. Dopamine enables cell communication. Abnormal regulation of the molecule is associated with a variety of diseases such as Parkinson’s disease, Attention Deficit Hyperactivity Disorder (ADHD), and schizophrenia among others.
Chen and his team then tested effects of dopamine antagonists glioblastoma and observed that the drugs exerted significant anti-tumor effects. These are synergistic when used in combination with other anti-glioblastoma drugs when inhibiting growth of tumors. Chen called the anti-glioblastoma effects of the drugs as ‘unexpected.’
Bob Carter, chairman of division of neurosurgery, UC San Diego School of Medicine, said “On the clinical front, the finding is important for two reasons. First, these drugs are already FDA-cleared for human use in the treatment of other diseases, so it is possible these drugs may be re-purposed for glioblastoma treatment, thereby bypassing years of pre-clinical testing. Second, these drugs have been shown to cross the blood-brain barrier, a barrier that prevents more than 90 percent of drugs from entry into the brain.”
The researchers’ findings were published online in Oncotarget.