Therapeutic targeting of EPH receptors and their ligands

被引:281
作者
Boyd, Andrew W. [1 ]
Bartlett, Perry F. [2 ]
Lackmann, Martin [3 ]
机构
[1] Queensland Inst Med Res, Leukaemia Fdn Res Lab, Brisbane, Qld 4029, Australia
[2] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
[3] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia
基金
英国科研创新办公室;
关键词
TYROSINE KINASE EPHB4; SPINAL-CORD-INJURY; GROWTH-FACTOR RECEPTOR; CELL-LUNG-CANCER; UP-REGULATION; PROSTATE-CANCER; AXONAL REGENERATION; TUMOR-SUPPRESSOR; BREAST-CANCER; STEM-CELLS;
D O I
10.1038/nrd4175
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Critical roles for EPH receptor (EPH)-ephrin signalling in a range of chronic and regenerative diseases are increasingly being recognized. In particular, the complex roles of EPHs and ephrins in tumour growth and progression, and in nerve injury and regeneration have been studied extensively. This has led to considerable progress in developing strategies for their therapeutic targeting, with some anticancer agents already in clinical trials. Promising leads for non-malignant diseases are also emerging, with compelling preclinical data encouraging clinical development. We discuss this rapidly developing area of drug discovery, highlighting the associated challenges and limitations.
引用
收藏
页码:39 / 62
页数:24
相关论文
共 305 条
[1]   Axon Guidance Molecules in Vascular Patterning [J].
Adams, Ralf H. ;
Eichmann, Anne .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2010, 2 (05) :a001875
[2]   Eph receptors and ephrin ligands: Essential mediators of vascular development [J].
Adams, RH ;
Klein, R .
TRENDS IN CARDIOVASCULAR MEDICINE, 2000, 10 (05) :183-188
[3]   Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis [J].
Adams, RH ;
Wilkinson, GA ;
Weiss, C ;
Diella, F ;
Gale, NW ;
Deutsch, U ;
Risau, W ;
Klein, R .
GENES & DEVELOPMENT, 1999, 13 (03) :295-306
[4]   Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors [J].
Alazzouzi, H ;
Davalos, V ;
Kokko, A ;
Domingo, E ;
Woerner, SM ;
Wilson, AJ ;
Konrad, L ;
Laiho, P ;
Espín, E ;
Armengol, M ;
Imai, K ;
Yamamoto, H ;
Mariadason, JM ;
Gebert, JF ;
Aaltonen, LA ;
Schwartz, S ;
Arango, D .
CANCER RESEARCH, 2005, 65 (22) :10170-10173
[5]   The Eph/ephrinB signal balance determines the pattern of T-cell maturation in the thymus [J].
Alfaro, David ;
Jose Munoz, Juan ;
Garcia-Ceca, Javier ;
Cejalvo, Teresa ;
Jimenez, Eva ;
Zapata, Agustin G. .
IMMUNOLOGY AND CELL BIOLOGY, 2011, 89 (08) :844-852
[6]  
Allan EH, 2008, J BONE MINER RES, V23, P1170, DOI [10.1359/jbmr.080324, 10.1359/JBMR.080324]
[7]   Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth [J].
Angeles Abengozar, Maria ;
de Frutos, Sergio ;
Ferreiro, Sergio ;
Soriano, Joaquim ;
Perez-Martinez, Manuel ;
Olmeda, David ;
Marenchino, Marco ;
Canamero, Marta ;
Ortega, Sagrario ;
Megias, Diego ;
Rodriguez, Antonio ;
Martinez-Torrecuadrada, Jorge L. .
BLOOD, 2012, 119 (19) :4565-4576
[8]   Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors [J].
Annunziata, Christina M. ;
Kohn, Elise C. ;
LoRusso, Patricia ;
Houston, Nicole D. ;
Coleman, Robert L. ;
Buzoianu, Manuela ;
Robbie, Gabriel ;
Lechleider, Robert .
INVESTIGATIONAL NEW DRUGS, 2013, 31 (01) :77-84
[9]   Expression Profile and Role of EphrinA1 Ligand After Spinal Cord Injury [J].
Arocho, Luz C. ;
Figueroa, Johnny D. ;
Torrado, Aranza I. ;
Santiago, Jose M. ;
Vera, Ariel E. ;
Miranda, Jorge D. .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 2011, 31 (07) :1057-1069
[10]   Eph/ephrin signaling: networks [J].
Arvanitis, Dina ;
Davy, Alice .
GENES & DEVELOPMENT, 2008, 22 (04) :416-429