Mechanisms of drug inhibition of signalling molecules

被引:243
作者
Sebolt-Leopold, Judith S.
English, Jessie M.
机构
[1] Pfizer Global Res & Dev, Michigan Labs, Ann Arbor, MI 48105 USA
[2] Pfizer Res Technol Ctr, Cambridge, MA 02139 USA
关键词
D O I
10.1038/nature04874
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The emergence of tumour-specific, molecularly targeted agents signifies a paradigm shift in cancer therapy, with less reliance on drugs that non-discriminately kill tumour and host cells. Although the diversity of targets giving rise to this new generation of anticancer drugs has expanded, many challenges persist in the design of effective treatment regimens. The complex interplay of signal-transduction pathways further complicates the customization of cancer treatments to target single mechanisms. However, despite uncertainty over precise or dominant mechanisms of action, especially for compounds targeting multiple gene products, emerging agents are producing significant therapeutic advances against a broad range of human cancers.
引用
收藏
页码:457 / 462
页数:6
相关论文
共 58 条
[31]  
Kostich M, 2002, GENOME BIOL, V3
[32]   EVIDENCE THAT TRANSFORMING GENE OF AVIAN-SARCOMA VIRUS ENCODES A PROTEIN-KINASE ASSOCIATED WITH A PHOSPHOPROTEIN [J].
LEVINSON, AD ;
OPPERMANN, H ;
LEVINTOW, L ;
VARMUS, HE ;
BISHOP, JM .
CELL, 1978, 15 (02) :561-572
[33]   Discovery of a novel Raf kinase inhibitor [J].
Lyons, JF ;
Wilhelm, S ;
Hibner, B ;
Bollag, G .
ENDOCRINE-RELATED CANCER, 2001, 8 (03) :219-225
[34]   The protein kinase complement of the human genome [J].
Manning, G ;
Whyte, DB ;
Martinez, R ;
Hunter, T ;
Sudarsanam, S .
SCIENCE, 2002, 298 (5600) :1912-+
[35]  
Mendel DB, 2003, CLIN CANCER RES, V9, P327
[36]   Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma [J].
Motzer, RJ ;
Michaelson, MD ;
Redman, BG ;
Hudes, GR ;
Wilding, G ;
Figlin, RA ;
Ginsberg, MS ;
Kim, ST ;
Baum, CM ;
DePrimo, SE ;
Li, JZ ;
Bello, CL ;
Theuer, CP ;
George, DJ ;
Rini, BI .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (01) :16-24
[37]   Lapatinib: A novel dual tyrosine kinase inhibitor with activity in solid tumors [J].
Nelson, MH ;
Dolder, CR .
ANNALS OF PHARMACOTHERAPY, 2006, 40 (02) :261-269
[38]   Targeted CML therapy: controlling drug resistance, seeking cure [J].
O'Hare, T ;
Corbin, AS ;
Druker, BJ .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2006, 16 (01) :92-99
[39]   Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition [J].
Ohren, JF ;
Chen, HF ;
Pavlovsky, A ;
Whitehead, C ;
Zhang, EL ;
Kuffa, P ;
Yan, CH ;
McConnell, P ;
Spessard, C ;
Banotai, C ;
Mueller, WT ;
Delaney, A ;
Omer, C ;
Sebolt-Leopold, J ;
Dudley, DT ;
Leung, IK ;
Flamme, C ;
Warmus, J ;
Kaufman, M ;
Barrett, S ;
Tecle, H ;
Hasemann, CA .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2004, 11 (12) :1192-1197
[40]   Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site [J].
Pargellis, C ;
Tong, L ;
Churchill, L ;
Cirillo, PF ;
Gilmore, T ;
Graham, AG ;
Grob, PM ;
Hickey, ER ;
Moss, N ;
Pav, S ;
Regan, J .
NATURE STRUCTURAL BIOLOGY, 2002, 9 (04) :268-272