“Glioblastoma multiforme (GBM) is the most aggressive brain cancer with no cure. Chemotherapy resistance has limited the use of temozolamide, a drug used to prolong the life of these patients,” said Martyn Sharpe, Ph.D., associate research professor of neurosurgery at Houston Methodist Hospital and a senior investigator on the study. “In an animal model of human brain cancer, combining the smart drug with chemotherapy prolonged life by over six fold.”
In research findings presented at the Society for Neuro-Oncology annual conference, a team of researchers led by scientist Sharpe and neurosurgeon David S. Baskin, M.D. director of the Kenneth R. Peak Brain and Pituitary Tumor Center at Houston Methodist Hospital invented a targeted way to overcome chemotherapy drug resistance and destroy the deadliest brain tumors while sparing surrounding brain tissue.
Results from the study showed that the smart drug is nontoxic in normal cells but transformed in GBM cells into a compound that blocks chemotherapy resistance, allowing for the destruction of aggressive brain cancer cells.
GBM and other brain cancers express high levels of a protein termed Monoamine oxidase B or MAOB, which converts the inactive drug into a compound that prevents chemotherapy resistance.
These results support further testing of PAM-OBG as a potential drug candidate for the treatment of patients with GBM or other cancers with high MAOB protein levels.