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
[1]   Activation loop phosphorylation and catalysis in protein kinases: Is there functional evidence for the autoinhibitor model? [J].
Adams, JA .
BIOCHEMISTRY, 2003, 42 (03) :601-607
[2]   Allosteric inhibitors of Bcr-abl-dependent cell proliferation [J].
Adrián, FJ ;
Ding, Q ;
Sim, TB ;
Velentza, A ;
Sloan, C ;
Liu, Y ;
Zhang, GB ;
Hur, W ;
Ding, S ;
Manley, P ;
Mestan, J ;
Fabbro, D ;
Gray, NS .
NATURE CHEMICAL BIOLOGY, 2006, 2 (02) :95-102
[3]   The specificities of protein kinase inhibitors: an update [J].
Bain, J ;
McLauchlan, H ;
Elliott, M ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2003, 371 :199-204
[4]   Critical update and emerging trends in epidermal growth factor receptor targeting in cancer [J].
Baselga, J ;
Arteaga, CL .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (11) :2445-2459
[5]   Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors [J].
Bergers, G ;
Song, S ;
Meyer-Morse, N ;
Bergsland, E ;
Hanahan, D .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (09) :1287-1295
[6]   Oncogenic kinase signalling [J].
Blume-Jensen, P ;
Hunter, T .
NATURE, 2001, 411 (6835) :355-365
[7]   IDENTIFICATION OF A TRANSFORMATION-SPECIFIC ANTIGEN-INDUCED BY AN AVIAN-SARCOMA VIRUS [J].
BRUGGE, JS ;
ERIKSON, RL .
NATURE, 1977, 269 (5626) :346-348
[8]   Activation mechanism of the MAP kinase ERK2 by dual phosphorylation [J].
Canagarajah, BJ ;
Khokhlatchev, A ;
Cobb, MH ;
Goldsmith, EJ .
CELL, 1997, 90 (05) :859-869
[9]   New paradigms for the treatment of cancer: The role of anti-angiogenesis agents [J].
Cherrington, JM ;
Strawn, LM ;
Shawver, LK .
ADVANCES IN CANCER RESEARCH, VOL 79, 2000, 79 :1-38
[10]   FDA drug approval summary:: Gefitinib (ZD1839) (Iressa®) tablets [J].
Cohen, MH ;
Williams, GA ;
Sridhara, R ;
Chen, G ;
Pazdur, R .
ONCOLOGIST, 2003, 8 (04) :303-306