Primary brain tumors account for less than 2% of all
cancers in adults; however, they are often associated with neurologic morbidity and high mortality.
Glioblastoma multiforme (GBM) has been a focus of new
therapy development in neurooncology because it is the most common
primary brain tumor in adults. Standard-of-care
therapy for newly diagnosed GBM includes surgical resection,
radiotherapy, and
temozolomide, administered both during and after
radiotherapy. However, most patients develop
tumor recurrence or progression after this multimodality treatment. Repeat resection and stereotactic radiosurgery upon recurrence may improve outcome only in selected patients. Most salvage
chemotherapies offer only palliation. Recent advances in our understanding of the molecular abnormalities of GBM have generated new therapeutic venues of molecularly targeted agents (
designer drugs) against key components of cellular pathways critical for
cancer initiation and maintenance. Such drugs may offer the potential advantage to increase therapeutic efficacy and decrease systemic toxicity compared with traditional
cytotoxic agents. Nonetheless, first-generation targeted agents have failed to demonstrate survival benefits in unselected GBM patient populations. Several mechanisms of treatment failure of the first-generation
designer drugs have been proposed, whereas new strategies have been developed to increase effectiveness of these agents. Here we will discuss the recent development and the strategies to optimize the effectiveness of designer
therapy for GBM.