Treatment options for malignant gliomas, emphasizing towards new molecularly targeted therapies

Malignant gliomas (MGs), including glioblastomas and anaplastic astrocytomas are the most common primary brain tumors. Despite treatment advances, the outcome of patients diagnosed with MGs is poor. The current standard treatment protocols for managing these tumors include maximally safe surgical resection, followed by fractioned radiation therapy of the tumor and surrounding brain parenchyma. Until recently, the use of systemic chemotherapy was restricted and ineffective, due to the fact that the blood brain barrier inhibits the adequate therapeutic concentrations of most chemotherapeutic agents into the tumor and peritumoral area. Genetic transformation, like the expression or the DNA repair enzyme methylguanine methyltransferase (MGMT) and specific characteristics of these neoplasms are also causal factors, accounting for the development of treatment resistance to standard chemotherapy options with alkylating compounds. Recent advances, mostly, in thorough understanding of the complex molecular pathogenesis of MGs have led to arousal of rational development of new molecularly targeted treatment options that simultaneously affect multiple signalling pathways. Currently, several molecularly targeted agents, like tyrosine kinase and growth factor inhibitors have been tested in clinical trials to establish future directions in the therapy of MGs. A number of novel targeted strategies, including among others radio-immuno and ligand-toxin conjugates and RNA-based therapies, are also under investigation. We herein review and discuss the standard treatment options and recent advances in the therapy of MGs, with emphasis on the current knowledge towards the molecular pathogenesis of MGs as well as molecularly targeted therapies. We also highlight areas of future research. (C) 2008 Elsevier Ireland Ltd. All rights reserved.