Drug boosts effectiveness of radiation therapy for brain tumors
An enzyme inhibitor that helps repair DNA damage may provide a new way to improve the effectiveness of radiation therapy for a highly lethal type of brain cancer.
Glioblastoma--the most common and most aggressive type of brain tumor--originates from glial cells, which provide support for nerve cells and help regulate the internal environment of the brain. The average survival rate for glioblastoma is only about 15 months, but a combination of surgery followed by radiation therapy and chemotherapy may increase the chances of survival.
Scientists at Virginia Commonwealth University Massey Cancer Center tested an experimental drug, KU-60019, in mouse models of human glioblastoma multiforme to block the activation of ataxia telangiectasia mutated (ATM), an enzyme that helps repair DNA damage. Weakened by the enzyme inhibitor, the gliomas lost their ability to repair the DNA damage caused by the radiation treatment.
"By limiting the tumor's ability to combat DNA damage caused by treatments such as radiation, we are hopeful that we can enhance our ability to specifically target the glioma, prolong survival and reduce damage to surrounding brain tissue," said the study's lead researcher, Kristoffer Valerie, a professor in the Department of Radiation Oncology at VCU Massey Cancer Center.
In addition, the drug was particularly effective at combating gliomas that have a mutation in the p53 tumor-suppressor gene, which make up about 30% of all glioma cases. In mice with a human form of glioblastoma, the new drug significantly extended survival when combined with radiation therapy. The research was published in the journal Clinical Cancer Research.
The UVA researchers are not the only ones looking into the possibility of using enzyme inhibitors to enhance the effectiveness of glioblastoma treatments. New York-based CureFAKtor Pharmaceuticals is also working on an enzyme inhibitor that blocks focal adhesion kinase (FAK), an enzyme that is overexpressed in cancer cells.
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