However, even the concentrations of rapamycin in most GBM tissues were above the level known to confer anti-proliferative activity in PTEN-null cell lines in vitro (typically 1 nM), not every patient showed corresponding biological responses (determined by Ki-67), partially because of inadequate mTOR signaling inhibition (determined by S6 phosphorylation). This evidence concerns the gene PTEN and glioblastoma.