Dept. Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Curr Pharm Des. 2013;19(5):951-7.
Glioblastoma multiforme (GMB) is the most malignant and common type of all astrocytic tumors. Current standard of care entails maximum surgical resection of the tumor, followed by radiotherapy and chemotherapy, usually by the alkylating agent Temozolomide (TMZ). Despite this aggressive combination therapy, the survival rate of GBM patients is still low. Deregulation of the phosphatidylinositol 3-kinase (PI3K) / Akt pathway is a frequent occurrence in GBM. Activation of the PI3K-Akt pathway results in disturbance of control of cell growth and cell survival, which contributes to a competitive growth advantage, metastatic competence as well as to therapy resistance. The PI3K-Akt pathway is therefore an attractive therapeutic target in GBM, because it serves as a convergence point for malignant processes and intervention might overcome resistance to chemotherapy and radiation. The present review shows the importance of Akt in GBM and its role in the DNA damage response. Furthermore, an overview is given of specific inhibitors of Akt which are currently being tested in preclinical and in early phase clinical studies.
多形性胶质母细胞瘤（GBM）是所有星形细胞瘤中最恶性和最常见的类型。目前的治疗标准包括最大限度地切除肿瘤，然后进行放疗和化疗，通常使用烷化剂替莫唑胺（TMZ）。尽管采用了这种积极的联合治疗方法，GBM 患者的生存率仍然很低。PI3K/Akt 通路的失调在 GBM 中经常发生。PI3K-Akt 通路的激活导致细胞生长和细胞存活的失控，这有助于竞争生长优势、转移能力以及对治疗的耐药性。因此，PI3K-Akt 通路是 GBM 中一个有吸引力的治疗靶点，因为它是恶性过程的汇聚点，干预可能会克服对化疗和放疗的耐药性。本综述展示了 Akt 在 GBM 中的重要性及其在 DNA 损伤反应中的作用。此外，还概述了目前正在临床前和早期临床试验中测试的 Akt 特异性抑制剂。
