New methods to measure and interrupt metabolic fluxes in brain cancer

ABSTRACT Glioblastomas (GBMs) are deadly incurable brain cancers that are treated with resection followed by radiation, which is often combined with chemotherapy. GBMs rewire their metabolism to fuel their growth, invasion, survival and treatment resistance. Therapeutic strategies to block altered GBM metabolism are being translated into the clinic, however we do not know which metabolic strategy is optimal for the treatment of GBM patients. Further, we lack methods to directly measure metabolic activity in human brain cancers, which makes it difficult to determine which patients are likely to respond to which metabolic treatment strategy. In this research proposal, we will develop new methods to directly measure metabolic pathway activity in mouse models and patients with GBM. We will then perform a therapeutic clinical trial to evaluate the safety, on-target activity, and potential efficacy of a new metabolic strategy for the treatment of GBM.