Department of Neurooncology, National Center of Tumor Disease, University Clinic Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
Neuro Oncol. 2011 Jun;13(6):566-79. doi: 10.1093/neuonc/nor039.
Insights into the molecular pathogenesis of glioblastoma have not yet resulted in relevant clinical improvement. With standard therapy, which consists of surgical resection with concomitant temozolomide in addition to radiotherapy followed by adjuvant temozolomide, the median duration of survival is 12-14 months. Therefore, the identification of novel molecular targets and inhibitory agents has become a focus of research for glioblastoma treatment. Recent results of bevacizumab may represent a proof of principle that treatment with targeted agents can result in clinical benefits for patients with glioblastoma. This review discusses limitations in the existing therapy for glioblastoma and provides an overview of current efforts to identify molecular targets using large-scale screening of glioblastoma cell lines and tumor samples. We discuss preclinical and clinical data for several novel molecular targets, including growth factor receptors, phosphatidylinositol-3 kinase, SRC-family kinases, integrins, and CD95 ligand and agents that inhibit these targets, including erlotinib, enzastaurin, dasatinib, sorafenib, cilengitide, AMG102, and APG101. By combining advances in tumor screening with novel targeted therapies, it is hoped that new treatment options will emerge for this challenging tumor type.
胶质母细胞瘤的分子发病机制研究尚未带来相关的临床改善。采用标准疗法，即手术切除联合替莫唑胺治疗，再辅以放疗和辅助替莫唑胺治疗，中位生存时间为 12-14 个月。因此，寻找新的分子靶点和抑制剂已成为胶质母细胞瘤治疗的研究重点。贝伐单抗的近期结果可能证明了一个原则，即针对特定靶点的治疗可以为胶质母细胞瘤患者带来临床获益。本文讨论了胶质母细胞瘤现有治疗方法的局限性，并概述了使用大规模胶质母细胞瘤细胞系和肿瘤样本筛选来鉴定分子靶点的当前努力。我们讨论了几个新的分子靶点的临床前和临床数据，包括生长因子受体、磷脂酰肌醇-3 激酶、Src 家族激酶、整合素、CD95 配体以及抑制这些靶点的药物，包括厄洛替尼、恩杂鲁胺、达沙替尼、索拉非尼、西仑吉肽、AMG102 和 APG101。通过将肿瘤筛选的进展与新型靶向治疗相结合，有望为这种具有挑战性的肿瘤类型带来新的治疗选择。
