Molecular target-based cancer therapy: tyrosine kinase inhibitors.
Improved understanding of tumor biology has led to the identification of numerous growth factors that are involved in malignant transformation and tumor progression. Many of these factors induce cellular responses through receptors with intrinsic tyrosine kinase (TK) activity. Therefore, inhibiting the activity of TK receptors is one of the ways to effectively block the disordered proliferation of cancer that arises from these pathways. The human epidermal growth factor receptor (HER) family is overexpressed or dysfunctional in many human malignancies. Therefore, these receptors have been identified as targets for cancer therapy. Several agents have been developed that reversibly or irreversibly inhibit one, two, or all of the HER receptors. Iressa and Tarceva are HER1-specific TK inhibitors that are in advanced development. The large phase II study of Iressa (IDEAL1) in patients with non-small-cell lung cancer (NSCLC) in whom previous platinum-based therapy has failed, found that the median survival time (MST) was 7.6 months, which was no less than that with Docetaxel treatment. Other dual or pan-HER, reversible or irreversible, TK inhibitors are being investigated in phase I trials. Early data show that they are generally well tolerated and have provided evidence of against activity tumors. HER-TK inhibitors are likely to have a substantial impact on the treatment of cancer patients.
Tamura
Kenji
K
Department of Medical Oncology, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan. tamura@med.kindai.ac.jp
Fukuoka
Masahiro
M
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018815:Genes, erbB / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases