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Designer therapies for glioblastoma multiforme.

Abstract
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.
AuthorsSith Sathornsumetee, Jeremy N Rich
JournalAnnals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1142 Pg. 108-32 (Oct 2008) ISSN: 1749-6632 [Electronic] United States
PMID18990124 (Publication Type: Journal Article, Review)
Chemical References
  • Designer Drugs
Topics
  • Brain Neoplasms (drug therapy)
  • Designer Drugs (pharmacology, therapeutic use)
  • Glioblastoma (drug therapy, physiopathology)
  • Humans
  • Models, Biological
  • Signal Transduction (drug effects)

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