Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents.
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 trade mark and Tarceva trade mark ), inhibitors of the split kinase domain receptor tyrosine kinase subgroup (e.g., PTK787/ZK 222584 and SU11248) and inhibitors of tyrosine kinases from multiple subgroups (e.g., Gleevec trade mark ). 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.
Laird
A Douglas
AD
Department of Preclinical Research and Exploratory Development, SUGEN, Inc., 230 E. Grand Avenue, South San Francisco, CA 94080, USA.
Cherrington
Julie M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000639:trends; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases