Malignant Gliomas

Malignant gliomas are characterized by rapid cell proliferation, high invasion and frequent genetic alterations. In spite of advances in multimodality therapy, with aggressive surgical resection combined with irradiation and chemotherapy, the median survival remains poor. Regardless of the genomic background of these tumors, a common feature is their poor response or acquired resistance to not only conventional cytotoxic chemotherapy agents, but also molecularly targeted agents that would be predicted to have efficacy based on the underlying genomic characteristics of the tumor. In collaboration with Dr. Pollack in the department of Neurological Surgery we are exploring the use of combination therapy approaches to understand the mechanisms of acquired resistance and identify effective therapeutic strategies to overcome the resistant phenotype in gliomas. As illustrated below, prolonged treatment with panobinostat, bortezomib, or both agents together leads to a notable decrease in apoptosis induction in comparison to treatment-naïve cells, as assessed by annexin staining, highlighting the induction of acquired treatment resistance in glioma cells.