Sant' Andrea Hospital, Department of Radiotherapy Oncology, Via di Grottarossa 1035, 00189 Roma, Italy.
Anticancer Res. 2009 Dec;29(12):5171-84.
Glioblastoma is the most frequent and devastating primary malignant brain tumor in adults. Surgery followed by standard radiotherapy with concomitant and adjuvant chemotherapy with temozolomide is the standard of care in patients with glioblastoma, however the prognosis remains poor with a median survival in the range of 12-15 months. Common genetic abnormalities in glioblastoma are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy. Special attention has been focused on targets such as epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and on pathways such as the phosphatidylinositol-3kinase/Akt/mammalian target of rapamycin and Ras/Raf/mitogen-activated protein-kinase pathways. Several signal transduction inhibitors have been examined in preclinical and clinical malignant glioma trials, including antiangiogenic agents (bevacizumab, enzastaurin), and inhibitors of epidermal growth factor receptor tyrosine kinase (gefitinib and erlotinib), mammalian target of rapamycin (temsirolimus, everolimus) and integrin (cilengitide). Although preliminary clinical results of the use of targeted agents have not translated into significantly better survival, more recent phase II trials are exploring the combination of multitargeted drugs with cytotoxic chemotherapy and radiotherapy in order to overcome the resistance of tumors to single-agent targeted therapies. This review summarizes the current results with cytotoxic and targeted molecular agents in glioblastoma and the development of new chemoradiation strategies under evaluation to increase their effectiveness.
胶质母细胞瘤是成年人中最常见和最具破坏性的原发性恶性脑肿瘤。手术联合标准放疗，同时使用替莫唑胺进行辅助化疗，是胶质母细胞瘤患者的标准治疗方法，然而，预后仍然很差，中位生存期在 12-15 个月之间。胶质母细胞瘤中的常见遗传异常与细胞信号转导途径的异常激活或抑制以及对放疗和化疗的耐药性有关。人们特别关注表皮生长因子受体、血管内皮生长因子受体、血小板衍生生长因子受体等靶点，以及磷脂酰肌醇-3 激酶/ Akt/哺乳动物雷帕霉素靶蛋白和 Ras/Raf/丝裂原激活蛋白激酶途径等途径。已经在临床前和恶性胶质瘤试验中研究了几种信号转导抑制剂，包括抗血管生成剂（贝伐单抗、恩扎妥林）和表皮生长因子受体酪氨酸激酶抑制剂（吉非替尼和厄洛替尼）、哺乳动物雷帕霉素靶蛋白（替西罗莫司、依维莫司）和整合素（西仑吉肽）。尽管靶向药物使用的初步临床结果并未转化为显著更好的生存，但最近的 II 期试验正在探索多靶点药物与细胞毒性化疗和放疗的联合应用，以克服肿瘤对单一靶向治疗的耐药性。这篇综述总结了在胶质母细胞瘤中使用细胞毒性和靶向分子药物的现有结果，以及正在评估的新的放化疗策略的发展，以提高其疗效。
