The combination of novel low molecular weight inhibitors of RAF (LBT613) and target of rapamycin (RAD001) decreases glioma proliferation and invasion.

Monotherapies have proven largely ineffective for the treatment of glioblastomas, suggesting that increased patient benefit may be achieved by combining therapies. Two protumorigenic pathways known to be active in glioblastoma include RAS/RAF/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT/target of rapamycin (TOR). We investigated the efficacy of a combination of novel low molecular weight inhibitors LBT613 and RAD001 (everolimus), which were designed to target RAF and TOR, respectively.

Malignant glioma drug discovery - targeting protein kinases.

Malignant gliomas are uncommon, but extremely lethal, cancers. Current standard-of-care includes surgery, radiation and chemotherapy, but recent research has generated a shift towards targeting the aberrant signal transduction components that underlie the pathogenesis of malignant gliomas. Protein kinases are a family of enzymes that are key elements in signal transduction-regulated cellular homeostasis subdivided based on their catalytic activity into tyrosine kinases and serine/threonine kinases.