Glioblastoma

Glioblastoma (GBM) is a disease that strikes without warning, often manifested by new onset seizure or a few days of progressive focal weakness, numbness, or headache, yet evaluation with MR imaging reveals a large mass that was likely present for months or years. Its stealth-like behavior belies the hallmark feature of this deadly cancer that it infiltrates normal brain diffusely over long distances without overt disruption of neuronal circuits early in the disease course, making it impossible to detect early or to cure surgically. The median survival time is 16 months with approximately 25% of patients alive at 2 years. The mainstay of treatment has remained unchanged over 15 years with maximum safe resection and concurrent oral alkylating agent, temozolomide, and external beam radiation. The GBM genome, transcriptome, methylome, and proteome have been extensively characterized, yet no molecular targeted therapies have yet proven effective in the clinic. Improvements in outcome for this devastating disease will require a better understanding of the pathophysiology and the development of robust preclinical models for testing new therapies.