Combined BH3 and Metabolic Profiling as a Method to Define Therapeutic Response and Resistance in Grade IV Astrocytomas

Background and SignificanceGrade IV astrocytomas, formerly known as glioblastoma multiforme (GBM), are the most common primary brain tumors and have the highest mortality. The therapeutic standard for managing this malignancy remains a combination of surgery, chemotherapy, and radiotherapy; however, there is no cure, nor has there been any significant advancement in the clinical approach to GBM since this protocol was established in 2005. This study aims to better understand the molecular and metabolic characteristics of GBM-derived cell lines to better define treatment groups and potentially identify new avenues for therapy. This study utilized continuous, commercially-available GBM cell lines U87, U118, A172, and H4, and GBM cell lines from the NCI60 bank (SF268, SF295, SF539, SNB19, SNB75 and U251) and examined the concentrations of Bcl-2 family proteins on mitochondria and metabolic activity for each of the cell lines. The measures were correlated to IC50 values for temozolomide (TMZ). ResultsWestern ...