New Investigator Grant Awarded to Nick Vitanza

The majority of DIPG lab models use tumor cells collected after a child’s death and, while generously donated and very important, those cells have been previously treated with chemotherapy and radiation so are not reflective of that child’s initial disease. At Seattle Children’s Hospital, we biopsy DIPG at diagnosis and implant these cells into mice at our lab at the Fred Hutch to create “treatment-naïve” DIPG mouse models, meaning an animal model that truly mimics the initial disease (as the tumor cells have not been exposed to radiation or chemotherapy). We also have discovered an effective new drug, quisinostat, that kills DIPG cells at low doses and targets specific cellular changes occurring due to DIPG’s histone mutation. We will test the benefit of this drug on treatment-naïve DIPG cells before, during, and after radiation to identify the most effective possible combination sequence of quisinostat and radiation. Furthermore, while quisinostat is in the same class as panobinostat, a drug already known to effectively kill DIPG cells, other agents in their class of “HDAC inhibitors” are ineffective. Now that we have two effective agents, we can hone in on their shared effects on tumor cells, which may prove vital to understanding and treating DIPG. Ultimately, as clinical trial models of giving a new drug during or after radiation have failed for decades, evaluating this promising agent and its sequence-specific effect with radiation in our “treatment-naïve” DIPG animal model can provide critical insights into this disease and form the foundation of more thoughtful and effective clinical trials.