Module Abstract

The Changing Landscape of Glioblastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) has been a focus of therapeutic development because it is the most common primary brain tumor in adults and is associated with neurologic morbidity and high mortality with median survival of only 15 months. Standard-of-care therapy for GBM includes surgical resection, radiotherapy, and temozolomide (during and after radiotherapy). However, most patients develop tumor recurrence or progression after multimodal treatment. Recent advances in our understanding of the molecular abnormalities of GBM have generated molecularly targeted agents against key components of cellular pathways critical for cancer initiation and maintenance. These agents may offer the therapeutic potential to increase efficacy compared with traditional cytotoxic agents. First-generation targeted agents, which inhibit only one or a few kinases, have failed to demonstrate survival benefits in unselected GBM patient populations. Several mechanisms of treatment failure of the first-generation targeted drugs have been proposed, whereas new strategies have been developed to increase effectiveness of these agents. This chapter summarizes the epidemiology, pathology, diagnosis, and therapeutic management of GBM, with a focus on therapy and recent advances to optimize the effectiveness of molecularly targeted agents for GBM.