The inhibitor of integrins Cilengitide: a new active drug in neuro-oncology

被引:3
作者
Leblond, Pierre [1 ]
Meignan, Samuel [2 ,3 ]
Le Tinier, Florence [2 ,3 ]
Bethe, Ullrich [4 ]
Lansiaux, Amelie [2 ,3 ]
机构
[1] Ctr Oscar Lambret, Unite Oncol Pediat, F-59020 Lille, France
[2] Univ Nord France, IMPRT, F-59020 Lille, France
[3] Ctr Oscar Lambret, Inst Rech Canc Lille, Lab Pharmacol Antitumorale, F-59020 Lille, France
[4] Lab Merck KGaA, D-64293 Darmstadt, Germany
关键词
Cilengitide; integrins; angiogenesis; targeted therapies; neuro-oncology; ADVANCED SOLID TUMORS; PHASE-I; MALIGNANT GLIOMA; BRAIN-TUMORS; ALPHA(V)BETA(3); ANGIOGENESIS; GLIOBLASTOMA; CELLS; RADIOTHERAPY; ANTAGONIST;
D O I
10.1684/bdc.2011.1429
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Last years saw the development of anti-angiogenic strategies in the treatment of cancers. Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) is a new drug targeting alpha v beta 3 and alpha v beta 5 integrins thanks to a specific peptide called RGD sequence. Cilengitide acts in correlations between endothelial cells, tumor cells and extracellular matrix. The promising results obtained with Cilengitide in vitro, used alone or in combination with cytotoxic chemotherapy or ionizing radiations, could give many hopes especially for the treatment of cerebral tumors. Clinical trials are nowadays ongoing in this indication. The aim of this review is to take stock of the situation on the mechanisms of action of the integrin inhibitor Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) with a focus on the first pre-clinical and clinical results.
引用
收藏
页码:1083 / 1090
页数:8
相关论文
共 38 条
[1]   Inhibition of αvβ3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy [J].
Abdollahi, A ;
Griggs, DW ;
Zieher, H ;
Roth, A ;
Lipson, KE ;
Saffrich, R ;
Gröne, HJ ;
Hallahan, DE ;
Reisfeld, RA ;
Debus, J ;
Niethammerl, AG ;
Huber, PE .
CLINICAL CANCER RESEARCH, 2005, 11 (17) :6270-6279
[2]   Integrin αVβ3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models [J].
Albert, Jeffrey M. ;
Cao, Carolyn ;
Ling Geng ;
Leavitt, Lauren ;
Hallahan, Dennis E. ;
Bo Lu .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 65 (05) :1536-1543
[3]   Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion [J].
Bellail, AC ;
Hunter, SB ;
Brat, DJ ;
Tan, C ;
Van Meir, EG .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2004, 36 (06) :1046-1069
[4]   REQUIREMENT OF VASCULAR INTEGRIN ALPHA(V)BETA(3) FOR ANGIOGENESIS [J].
BROOKS, PC ;
CLARK, RAF ;
CHERESH, DA .
SCIENCE, 1994, 264 (5158) :569-571
[5]  
Burke PA, 2002, CANCER RES, V62, P4263
[6]   Human malignant glioma therapy using anti-αvβ3 integrin agents [J].
Chatterjee, S ;
Matsumura, A ;
Schradermeier, J ;
Gillespie, GY .
JOURNAL OF NEURO-ONCOLOGY, 2000, 46 (02) :135-144
[7]   N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists [J].
Dechantsreiter, MA ;
Planker, E ;
Mathä, B ;
Lohof, E ;
Hölzemann, G ;
Jonczyk, A ;
Goodman, SL ;
Kessler, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (16) :3033-3040
[8]   Integrins in cancer: biological implications and therapeutic opportunities [J].
Desgrosellier, Jay S. ;
Cheresh, David A. .
NATURE REVIEWS CANCER, 2010, 10 (01) :9-22
[9]   An integrin αvβ3-c-Src oncogenic unit promotes anchorage-independence and tumor progression [J].
Desgrosellier, Jay S. ;
Barnes, Leo A. ;
Shields, David J. ;
Huang, Miller ;
Lau, Steven K. ;
Prevost, Nicolas ;
Tarin, David ;
Shattil, Sanford J. ;
Cheresh, David A. .
NATURE MEDICINE, 2009, 15 (10) :1163-U89
[10]   Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis [J].
Ebos, John M. L. ;
Lee, Christina R. ;
Cruz-Munoz, William ;
Bjarnason, Georg A. ;
Christensen, James G. ;
Kerbel, Robert S. .
CANCER CELL, 2009, 15 (03) :232-239