Glioblastoma multiforme (GBM) is by far the most common type of primary brain tumors and regarded as grade IV tumors by WHO classification. Although the treatment strategies including maximal surgical resection, concurrent radiation and chemotherapy with temozolomide are current recommendations to patients with GBM, the prognosis is still poor and the median survival is less than 2 years. Major challenge for the successful treatment of GBM is the diversity of cell types and mutations in the tumor. These tumors are composed of highly heterogeneous cell populations that are often characterized by high chemo-resistance. Furthermore, because a variety of genes may be mutated or overexpressed in different areas of the tumors, no one treatment is likely to destroy the tumor. With advance in the molecular biology in the field of oncology, new critical signaling pathway involved in development and progression of GBM have been discovered, which leads to emergency of new treatment strategies to target these signaling pathways with the goal to increase specific efficacy. These targeted therapies hold the promise of providing new, more effective treatment options with minimal toxicity. In this review, we described current chemotherapeutic modalities for GBM and introduce the new targeted therapies in the context of current treatment options for patients with GBM. In addition, it is also addressed the issue of drug delivery as a factor limiting the efficacy of systemic administration of therapeutics and attempt to overcome this barrier. To improve outcomes of treatment for GBM, future investigation will focus on elucidating the novel molecular signaling pathways and oncogenic mechanisms underlying tumor resistance to treatment and tumor recurrence.
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