Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development.
Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development.
复制标题
使用 PI3K 抑制剂治疗多形性胶质母细胞瘤的最新进展：当前的临床前和临床开发。
DOI：
10.1186/s12943-017-0670-3
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发表时间：
2017-06-07
期刊：
影响因子：
37.3
通讯作者：
Li WP
中科院分区：
文献类型：
--
作者：
Zhao HF;Wang J;Shao W;Wu CP;Chen ZP;To ST;Li WP
多形性胶质母细胞瘤是中枢神经系统最常见、侵袭性最强的原发肿瘤。治疗GBM最广泛使用的化疗药物之一是替莫唑胺，它是一种DNA烷基化试剂，其疗效取决于MGMT甲基化状态。在过去的十年中，在改善GBM患者预后方面进展甚微，这促使更有效的分子靶向治疗方法的发展。磷脂酰肌醇3-激酶(PI3K)/Akt通路的高激活常见于包括GBM在内的多种肿瘤中，它在调节肿瘤细胞的存活、生长、运动、血管生成和代谢中起着核心作用。许多PI3K抑制剂，包括PAN-PI3K、异构体选择性和双重PI3K/哺乳动物靶标雷帕霉素(MTOR)抑制剂已经显示出良好的临床前效果，并进入了一系列血液系统恶性肿瘤和实体瘤的临床试验。此外，针对PI3K的抑制剂与其他相关途径的联合应用可能在抑制肿瘤生长和改善患者预后方面发挥协同作用。目前，只有少数几种PI3K抑制剂处于治疗GBM的I/II期临床试验中。本文就PI3K/Akt通路在GBM中的重要作用作一综述，并对PI3K抑制剂单独或与其他抑制剂联合治疗GBM从临床前到临床的研究进展作一综述。
Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients’ prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.