期刊
FUTURE ONCOLOGY
卷 7, 期 3, 页码 339-354出版社
FUTURE MEDICINE LTD
DOI: 10.2217/FON.11.8
关键词
angiogenesis; glioblastoma; integrins; malignant glioma; VEGF
类别
资金
- Merck/Schering-Plough
- Roche/Genentech
- Merck KGaA/EMD Serono
- Merck KGaA
- Merck Serono
- Oncomethylome Sciences
- Roche
- Essex
- Schering-Plough/Merck Co.
- OncoMethylomeSciences
Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks alpha v beta 3 and alpha v beta 5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study (Cilengitide in Combination With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma Phase III Randomized Clinical Trial (CENTRIC)) for newly diagnosed GBM. In addition, randomized controlled Phase II studies with cilengitide are ongoing for non-small-cell lung cancer and squamous cell carcinoma of the head and neck. Cilengitide is the first integrin inhibitor in clinical Phase III development for oncology.
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