Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents

被引:76
作者
Laird, AD [1 ]
Cherrington, JM [1 ]
机构
[1] SUGEN Inc, Dept Preclin Res & Exploratory Dev, San Francisco, CA 94080 USA
关键词
Bcr-Abl; cancer; EGFR; FGFR; Flt-3; HER2; inhibitor; KIT; leukaemia; maximum tolerated dose; Met; PDGFR; receptor; Src; Tie-2; tyrosine kinase; VEGFR;
D O I
10.1517/eoid.12.1.51.21253
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Numerous small molecule synthetic tyrosine kinase inhibitors are in clinical development for the treatment of human cancers. These fall into three broad categories: inhibitors of the epidermal growth factor receptor tyrosine kinase family (e.g., Iressa(Tm) and Tarceva(TM)), inhibitors of the split kinase domain receptor tyrosine kinase subgroup (e.g., PTK787/ZK 222584 and SU1 1248) and inhibitors of tyrosine kinases from multiple subgroups (e.g., Gleevec(TM)). In addition, agents targeting other tyrosine kinases implicated in cancer, such as Met, Tie-2 and Src, are in preclinical development. As experience is gained in the clinic, it has become clear that unleashing the full therapeutic potential of tyrosine kinase inhibitors will require patient preselection, better assays to guide dose selection, knowledge of mechanism-based side effects and ways to predict and overcome drug resistance.
引用
收藏
页码:51 / 64
页数:14
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