EGFR tyrosine kinase inhibitor "gefitinib (Iressa)" for cancer therapy.
Nihon Yakurigaku Zasshi
; 122(6): 491-7, 2003 12.
Article
em Ja
| MEDLINE
| ID: mdl-14639003
ABSTRACT
Many malignant tumors including non-small cell lung cancer (NSCLC) express or over-express EGFR that have shown correlations with rapid growth, metastases, resistance to conventional chemotherapy or radiotherapy, and poor prognosis. Gefitinib is a potent and selective inhibitor of EGFR tyrosine kinase (EGFRTK). Gefitinib specifically inhibited EGF-stimulated cell proliferation in vitro and it also exhibited a broad anti-tumor spectrum against NSCLC, prostate, colorectal, and ovarian cancers in vivo. Gefitinib showed dose-dependent and reversible reduction of c-fos mRNA level and decreased Ki67 significantly in tumors in vivo. In in vitro studies, gefitinib arrested the cell cycle at G1 phase by inducing intrinsic cyclin-dependent kinase (cdk) inhibitors and following inhibition of cdk2. Apoptosis was also seen in gefitinib-treated tumor cells and skin biopsy samples from clinical study. Gefitinib inhibited VEGF production in tumor cells through inhibition of EGFR signaling, leading to suppression of angiogenesis. In clinical studies, gefitinib demonstrated therapeutic benefit in patients who failed conventional chemotherapy. No correlation has been established between the anti-tumor activity of gefitinib and EGFR expression level, whilst sensitivity factors to gefitinib are yet to be elucidated. Identification of sensitivity factors will be a key for effective use of EGFRTK inhibitors including gefitinib for cancer treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Proteínas Tirosina Quinases
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Inibidores Enzimáticos
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Fator de Crescimento Epidérmico
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
Ja
Revista:
Nihon Yakurigaku Zasshi
Ano de publicação:
2003
Tipo de documento:
Article