Multitargeted therapy: Can promiscuity be praised in an era of political correctness?

被引:45
作者
Jimeno, Antonio [1 ]
Hidalgo, Manuel [1 ]
机构
[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
关键词
EGFR; MAPK; promiscuous agents; targeted therapies; dual targeting;
D O I
10.1016/j.critrevonc.2006.01.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The rapidly expanding knowledge of the pathogenesis of cancer at the molecular level is providing new targets for drug discovery and development. However, cancer is a complex disease characterized,by multiple genetic and molecular alterations affecting cell proliferation, survival, differentiation and invasion among others. Many of these alterations represent potential targets for the development of new anticancer therapeutics. Because of the enormous biological diversity of cancer, it is unlikely that attacking only one of these targets will eliminate a malignant cell. Rather, strategic combination of agents targeted against the most critical of those alterations will be needed. Another approach that is rendering promising clinical results is the use of more unspecific agents that inhibit or modulate several relevant targets simultaneously. A deep biologic understanding of the relative relevance of each target in different cancer types will be key to efficiently direct those drugs to diseases more likely to benefit from its particular modulation profile. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:150 / 158
页数:9
相关论文
共 57 条
[1]
Akimoto T, 1999, CLIN CANCER RES, V5, P2884
[2]
Cl-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK) [J].
Allen, LF ;
Sebolt-Leopold, J ;
Meyer, MB .
SEMINARS IN ONCOLOGY, 2003, 30 (05) :105-116
[3]
Belanger M, 2003, P AN M AM SOC CLIN, V22, P244
[4]
Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors [J].
Bianco, R ;
Shin, I ;
Ritter, CA ;
Yakes, FM ;
Basso, A ;
Rosen, N ;
Tsurutani, J ;
Dennis, PA ;
Mills, GB ;
Arteaga, CL .
ONCOGENE, 2003, 22 (18) :2812-2822
[5]
Blackwell KL, 2004, J CLIN ONCOL, V22, p196S
[6]
Burris HA, 2003, P AN M AM SOC CLIN, V22, P248
[7]
Administration of CI-1033, an irreversible Pan-erbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: A phase I pharmacokinetic and food effect study [J].
Calvo, E ;
Tolcher, AW ;
Hammond, LA ;
Patnaik, A ;
de Bono, JS ;
Eiseman, IA ;
Olson, SC ;
Lenehan, PF ;
McCreery, H ;
LoRusso, P ;
Rowinsky, EK .
CLINICAL CANCER RESEARCH, 2004, 10 (21) :7112-7120
[8]
Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer [J].
Campos, S ;
Hamid, C ;
Seiden, MV ;
Oza, A ;
Plante, M ;
Potkul, RK ;
Lenehan, PF ;
Kaldjian, EP ;
Varterasian, ML ;
Jordan, C ;
Charbonneau, C ;
Hirte, H .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (24) :5597-5604
[9]
Chakravarti A, 2002, CANCER RES, V62, P200
[10]
Chen Z, 2000, ANTICANCER RES, V20, P899