Cancer is a disease characterized by the up-regulation of cell growth and it usually develops when normal cells are not able to repair damaged genetic material. New studies are revealing insights into the function of genetic mutations commonly found in a form of brain cancer, specifically the IDH mutation. Isocitrate Dehydrogenase(IDH) is a metabolic enzyme found in more than 70% of low grade gliomas and secondary glioblastomas, types of malignant brain tumors. In a normal cell, IDH enzymes help to break down nutrients and generate energy cells. When mutated, IDH creates a molecule that alters cells genetic programming and instead of maturing, the cell remain primitive. Studies have shown that cells holding this mutation also have an impaired ability to repair DNA. Strangely enough, low grade gliomas that have the IDH mutation are typically more sensitive to chemotherapy than those that lack the mutation. Why does this occur? We still don’t really know the answer. Yet, researchers have discovered a potential new treatment option for the glial cells harvesting the IDH mutation– PARP Inhibitors. A super cool future is waiting ahead.
When treating the IDH mutated cells with PARP Inhibitors, a substance in the form of a drug that blocks an enzyme called PARP, the cells were effectively killed. When the drug blocks PARP, it keeps the cancer cells from repairing their damaged DNA, and eventually they die off. The cells are extremely sensitive after the effects of the inhibitors, especially after taking the most common PARP drug called oliparib. PARP inhibitors are a form of targeted therapy–meaning the inhibitors work within a similar approach as radiation and chemotherapy– they simply damage or prevent the repair the DNA. Researchers have also found the up regulation of the unusual molecule called 2-HG(2-Hydroxyl-glutarate) within the IDH mutated enzymes. In a study with Dr. Brinda’s team at Yale, they found that 2-HG may be responsible for the defect, DNA repair inabilities, in these cells. When the production of 2-HG was blocked in these cells, the DNA repair defect was reversed and cells became unresponsive to the PARP inhibitor treatment. This finding further solidifies that PARP inhibitors may be the best new effective brain cancer treatment method. What do you think? I think this is pretty cool news!
There are also many clinical trials occurring currently to observe 2-HG as a definite IDH biomarker for cells that are sensitive to treatment with PARP inhibitors. In addition, labs are also designing a clinical trial of olaparib and temozolomide, two PARB inhibitor drugs, in patients with low-grade gliomas. The results of these trials, are for sure going to make headlines within the Biology and Medical field! Even though, there are still many questions to answers and studies to conduct regarding brain cancer and the IDH mutation, we are definitely on the right track to cure the monster a.k.a “cancer.”