Biomaterial platforms to identify therapeutic targets in brain cancer

Glioblastoma (GBM) is the most common primary intracranial tumor, with a dismal median survival time of less than two years. GBM is defined in part by extensive cellular infiltration into the three-dimensional tissue of the brain, destroying critical brain structures and rendering complete tumor eradication impossible. The search for therapies that limit invasion has been limited by a lack of culture paradigms that recapitulate important aspects of brain matrix while allowing high-resolution characterization of invasive cells. I will describe our team’s efforts to introduce and exploit such models, including our use of three-dimensional hyaluronic acid matrices to grow tumors in vitro, isolate invasive tumor cells, and identify targetable lesions that drive invasion. An important strength of these approaches is the ability to benchmark findings against site-directed biopsies from patients to ensure maximal clinical relevance.