The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells Journal Article
| Authors: | Moasser, M. M.; Basso, A.; Averbuch, S. D.; Rosen, N. |
| Article Title: | The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells |
| Abstract: | The epidermal growth factor receptor (EGFR) is commonly overexpressed in many human tumors and provides a new target for anticancer drug development. ZD1839 ("Iressa"), a quinazoline tyrosine kinase inhibitor selective for the EGFR, has shown good activity in preclinical studies and in the early phase of clinical trials. However, because it remains unclear which tumor types are the best targets for treatment with this agent, the molecular characteristics that correlate with tumor sensitivity to ZD1839 have been studied. In a panel of human breast cancer and other epithelial tumor cell lines, HER2-overexpressing tumors were particularly sensitive to ZD1839. Growth inhibition of these tumor cell lines was associated with the dephosphorylation of EGFR, HER2, and HER3, accompanied by the loss of association of HER3 with phosphatidylinositol 3-kinase, and down-regulation of Akt activity. These studies suggest that HER2-overexpressing tumors are particularly susceptible to the inhibition of HER family tyrosine kinase signaling and suggest novel strategies to treat these particularly aggressive tumors. |
| Keywords: | signal transduction; controlled study; protein expression; human cell; proto-oncogene proteins; clinical trial; drug activity; antineoplastic agents; cell division; controlled clinical trial; breast cancer; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor; down-regulation; receptor, epidermal growth factor; tumor cells, cultured; enzyme activity; protein tyrosine kinase; breast neoplasms; phosphorylation; phosphatidylinositol 3 kinase; protein tyrosine kinase inhibitor; cancer inhibition; antibodies, monoclonal; protein-serine-threonine kinases; tumor cell line; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; gefitinib; receptor, erbb-2; quinazolines; drug sensitivity; epithelium tumor; dephosphorylation; humans; human; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 61 |
| Issue: | 19 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2001-10-01 |
| Start Page: | 7184 |
| End Page: | 7188 |
| Language: | English |
| PUBMED: | 11585753 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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