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Integrins are critical intermediaries in a wide spectrum of cancer cell activities and thus represent a highly attractive target in oncology therapy. Nonetheless, successful exploitation of anti-integrin therapeutics has proven challenging to date for cancer patients. In this review, we will focus on cilengitide, an RGD pentapeptide inhibitor of α V integrins. Although several integrin inhibitors are under clinical evaluation, cilengitide is the most clinically advanced and is emerging as a prototype for this class of anticancer therapy. A foundation of encouraging preclinical studies led to a well-designed clinical development plan that culminated in a pivotal phase III study of cilengitide in combination with radiation therapy and temozolomide chemotherapy for newly diagnosed glioblastoma patients. Accrual to this study recently completed, while phase II studies of cilengitide are ongoing for head and neck cancer as well as lung cancer. Important future considerations for cilengitide and other integrin-targeting agents will likely include the identification of optimal combinatorial regimens and the delineation of biomarkers associated with efficacy.

Cilengitide: A Prototypic Integrin Inhibitor for the Treatment of Glioblastoma and Other Malignancies