A new study reveals that researchers studying a rare, always fatal brain tumor in children have found several molecular alterations that drive the cancer. The study was conducted by scientists at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and McGill University. The findings identify potential new targets for drug treatments.
The new research could help physicians choose targeted agents with a better chance of combating pediatric high-grade astrocytomas, which are extremely difficult to treat with radiation and surgery. The tumors have resisted treatment attempts with an estimated 250 chemotherapy drugs and combinations over the past 30 years, according to the investigators. Their study was published April 6 in Nature Genetics
The scientists sequenced tumor biopsy samples and identified a number of mutations or errors in the DNA code. They also found epigenetic changes, which alter how genes are expressed. At least two of the new mutations might be susceptible to blocking by existing drugs, said the investigators. Other molecular targets that they uncovered currently lack specific drugs to attack them but provide new opportunities for future drug development.
These results begin to crack open the genetic "black box" of these tumors, which only now are yielding clues to the abnormal molecular changes that drive them.
"For the most malignant tumor in pediatrics, we finally are beginning to gain a handle on the development of this disease, which is critical to devising effective therapies," says Mark Kieran, MD, PhD, a neuro-oncologist and clinical director of the Brain Tumor Center at Dana-Farber/Boston Children's. Kieran and neuropathologist Keith Ligon, MD, PhD, of Dana-Farber/Boston Children's, are co-senior authors along with two researchers from McGill.