Targeting the ERK signaling pathway in cancer therapy

被引:388
作者
Kohno, M
Pouyssegur, J
机构
[1] Nagasaki Univ, Lab Cell Regulat, Dept Pharmaceut Sci, Grad Sch Biomed Sci, Nagasaki 8528521, Japan
[2] Univ Nice, Inst Signaling Dev Biol & Canc Res, CNRS, UMR 6543, F-06108 Nice 2, France
关键词
anticancer drug; cancer; combination therapy; ERK pathway; MEK inhibitor; molecular targeted therapy; Raf inhibitor;
D O I
10.1080/07853890600551037
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The extracellular signal-regulated kinase (ERK) signaling pathway is a major determinant in the control of diverse cellular processes such as proliferation, survival, differentiation and motility. This pathway is often up-regulated in human tumors and as such represents an attractive target for the development of anticancer drugs. Because of its multiple roles in the acquisition of a complex malignant phenotype, specific blockade of the ERK pathway is expected to result in not only an anti-proliferative effect but also in anti-metastatic and anti-angiogenic effects in tumor cells. Recently potent small-molecule inhibitors targeting the components of the ERK pathway have been developed. Among them, BAY 43-9006 (Raf inhibitor), and PD184352, PD0325901 and ARRY-142886 (MEK1/2 inhibitors) have reached the clinical trial stage. We briefly discuss the possibility that combination of ERK pathway inhibitors (cytostatic agents) and conventional anticancer drugs (cytotoxic agents) provides an excellent basis for the development of new chemotherapeutic strategies against cancer.
引用
收藏
页码:200 / 211
页数:12
相关论文
共 72 条
[1]  
Arteaga CL, 2002, ONCOLOGIST, V7, P31
[2]   Signalling via the hypoxia-inducible factor-1α requires multiple posttranslational mofications [J].
Brahimi-Horn, C ;
Mazure, N ;
Pouysségur, J .
CELLULAR SIGNALLING, 2005, 17 (01) :1-9
[3]   Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors [J].
Clark, JW ;
Eder, JP ;
Ryan, D ;
Lathia, C ;
Lenz, HJ .
CLINICAL CANCER RESEARCH, 2005, 11 (15) :5472-5480
[4]   HOW MAP KINASES ARE REGULATED [J].
COBB, MH ;
GOLDSMITH, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (25) :14843-14846
[5]   Ras family signaling - Therapeutic targeting [J].
Cox, AD ;
Der, CJ .
CANCER BIOLOGY & THERAPY, 2002, 1 (06) :599-606
[6]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
Ewing, R ;
Floyd, Y ;
Gray, K ;
Hall, S ;
Hawes, R ;
Hughes, J ;
Kosmidou, V ;
Menzies, A ;
Mould, C ;
Parker, A ;
Stevens, C ;
Watt, S ;
Hooper, S ;
Wilson, R ;
Jayatilake, H ;
Gusterson, BA ;
Cooper, C ;
Shipley, J ;
Hargrave, D ;
Pritchard-Jones, K ;
Maitland, N ;
Chenevix-Trench, G ;
Riggins, GJ ;
Bigner, DD ;
Palmieri, G ;
Cossu, A ;
Flanagan, A ;
Nicholson, A ;
Ho, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954
[7]   Specificity and mechanism of action of some commonly used protein kinase inhibitors [J].
Davies, SP ;
Reddy, H ;
Caivano, M ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2000, 351 (351) :95-105
[8]   Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases [J].
Deng, XM ;
Ruvolo, P ;
Carr, B ;
May, WS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (04) :1578-1583
[9]  
Dent P, 2001, CLIN CANCER RES, V7, P775
[10]   Targeting ras signalling pathways in cancer therapy [J].
Downward, J .
NATURE REVIEWS CANCER, 2003, 3 (01) :11-22