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Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

DOI: 10.1186/1479-5876-7-77

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Malignant brain tumors consist of high-grade primary brain tumors such as malignant gliomas[1], and metastatic lesions to the brain from peripheral cancers such as lung, breast, renal, gastrointestinal tract, and melanoma[2,3]. Glioblastoma, the highest grade of malignant glioma, is the most common high-grade primary brain tumor in adults[4,5]. Overall, metastatic brain tumors are the most common brain tumors in adults, as 10% to 20% of patients with a malignant peripheral tumor develop brain metastases[2,3,6]. Even though malignant gliomas are generally treated with a combination of surgery, radiotherapy and systemic chemotherapy[7,8], and metastatic brain tumors with a combination of surgery and radiotherapy [9-11], the overall long-term prognosis of patients with these tumors, whether primary or metastatic, remains poor. Patient median survival times typically range between 3 and 16 months [12-16], and the percentage of patients alive at 5 years ranges between 3% and 10%[12,13,16,17]. In the treatment of both malignant gliomas and metastatic brain tumors, surgery and radiotherapy are more effective when used in combination[7-11,18-20]. In the treatment of malignant gliomas, there some minimal additional benefit of systemic chemotherapy[8,15,20-27]; and in the treatment of metastatic brain tumors, it remains unclear as to if there is any additional benefit of systemic chemotherapy[9,10,28-31].Systemic chemotherapy consists of small molecule chemotherapy drugs[8,32] that are drugs of molecular weights (MW) less than 1 kDa and diameters less than 1 to 2 nm. These small molecule chemotherapy drugs include traditional drugs that target the cell cycle, for example, DNA alkylating drugs, and newer investigational drugs that target cell surface receptors and associated pathways, for example, tyrosine kinase inhibitors[8,32]. The ineffectiveness of these chemotherapy drugs in treating malignant brain tumors has been attributed to the blood-brain barrier (BBB) being a sign


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