Cilengitide Treatment for Malignant Glioma: Current Status and Future Direction
Cilengitide Treatment for Malignant Glioma: Current Status and Future Direction
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DOI：
10.2176/nmc.52.539
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发表时间：
2012-08-01
影响因子：
1.9
通讯作者：
Date, Isao
中科院分区：
文献类型：
--
作者：
Kurozumi, Kazuhiko;Ichikawa, Tomotsugu;Date, Isao
恶性胶质瘤是最常见的原发性脑肿瘤，占大多数诊断。治疗包括手术、放疗和化疗，但这些方法很少能将患者的生命延长到诊断后一年以上。整合素在肿瘤细胞和肿瘤内皮细胞中表达，在胶质瘤的血管生成和侵袭中起重要作用。α v β 3和α v β 5整联蛋白调节细胞粘附，这些整联蛋白的抑制剂在某些临床前模型中抑制肿瘤生长。几种整合素靶向药物正在临床试验中作为治疗癌症的潜在化合物。其中，西仑吉肽是一种新型的整合素拮抗剂，用于治疗胶质母细胞瘤。多模式抗胶质瘤作用基于其细胞毒性、抗血管生成、抗侵袭和协同作用。临床前研究显示西仑吉肽和放化疗之间有希望的协同作用，以使肿瘤血管正常化和减弱肿瘤侵袭。目前正在评估Cilengitide在多形性胶质母细胞瘤患者的III期临床试验和其他类型癌症的II期临床试验中，迄今为止显示出有希望的治疗结果。这些和其他临床研究的结果是有很大的希望和兴趣。更清楚地了解每种方法的好处和陷阱，然后可以设计策略，从这些疗法中获得最大的好处。
Malignant glioma is the most common primary brain tumor and accounts for the majority of diagnoses. Treatment has involved a combination of surgery, radiation, and chemotherapy, yet these modalities rarely extend the life of the patient to more than one year from diagnosis. Integrins are expressed in tumor cells and tumor endothelial cells, and are important in angiogenesis and invasion in glioma. alpha v beta 3 and alpha v beta 5 integrins regulate cell adhesion, and inhibitors of these integrins suppress tumor growth in certain pre-clinical models. Several integrin-targeted drugs are in clinical trials as potential compounds for the treatment of cancer. Among them, cilengitide is a novel integrin antagonist for the treatment of glioblastoma. The multimodal anti-glioma effects are based on its cytotoxic, anti-angiogenic, anti-invasive, and synergetic effects. Preclinical studies showed a promising synergy between cilengitide and radiochemotherapy in order to normalize tumor vasculature and attenuate tumor invasion. Cilengitide is currently being assessed in phase III trials for patients with glioblastoma multiforme and in phase II trials for other types of cancers, demonstrating promising therapeutic outcomes to date. The results of these and other clinical studies are expected with great hope and interest. A more clear understanding of the benefits and pitfalls of each approach can then lead to the design of strategies to derive maximal benefit from these therapies.