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EnglishThe epidermal growth factor receptor (EGFR) is a cell membrane receptor that plays a key role in cancer development and progression. Ligand-activated EGFR-dependent signalling is involved in cell proliferation, apoptosis, angiogenesis and metastatic spread. Targeting the EGFR, therefore, represents a promising molecular approach in cancer treatment. Several anti-EGFR agents are in clinical development. Three drugs are currently in Phase II and III development as single agents, or in combination with other anticancer modalities: IMC-225 (cetuximab/Erbitux; ImClone), a chimaeric human-mouse monoclonal IgG(1) antibody, which blocks ligand binding and functional activation of the EGFR; OSI-774 (erlotinib/Tarceva; Genentech/OSI/Roch) and ZD1839 (gefitinib/Iressa; AstraZeneca), two small molecule EGFR-selective inhibitors of tyrosine kinase enzymatic activity, which prevent EGFR autophosphorylation and activation. Iressa is the first EGFR-targeting agent to be registered as an anticancer drug in Japan, in Australia and in the US for the third-line treatment of chemoresistant non-small cell lung cancer (NSCLC) patients. This review will focus on the preclinical background and on the results from the first series of clinical trials with these drugs. Furthermore, continuing clinical trials and a series of open clinical issues for the development of optimal strategies of using EGFR-targeting agents will be discussed.
Epidermal growth factor receptor tyrosine kinase inhibitors in late stage clinical trials. / FORTUNATO CIARDIELLO;FERDINANDO DE VITA;MICHELE ORDITURA;SABINO DE PLACIDO;G. TORTORA. - In: EXPERT OPINION ON EMERGING DRUGS. - ISSN 1472-8214. - 8(2003), pp. 501-514.
| Titolo: | Epidermal growth factor receptor tyrosine kinase inhibitors in late stage clinical trials. |
| Autori: | |
| Data di pubblicazione: | 2003 |
| Rivista: | |
| Citazione: | Epidermal growth factor receptor tyrosine kinase inhibitors in late stage clinical trials. / FORTUNATO CIARDIELLO;FERDINANDO DE VITA;MICHELE ORDITURA;SABINO DE PLACIDO;G. TORTORA. - In: EXPERT OPINION ON EMERGING DRUGS. - ISSN 1472-8214. - 8(2003), pp. 501-514. |
| Abstract: | The epidermal growth factor receptor (EGFR) is a cell membrane receptor that plays a key role in cancer development and progression. Ligand-activated EGFR-dependent signalling is involved in cell proliferation, apoptosis, angiogenesis and metastatic spread. Targeting the EGFR, therefore, represents a promising molecular approach in cancer treatment. Several anti-EGFR agents are in clinical development. Three drugs are currently in Phase II and III development as single agents, or in combination with other anticancer modalities: IMC-225 (cetuximab/Erbitux; ImClone), a chimaeric human-mouse monoclonal IgG(1) antibody, which blocks ligand binding and functional activation of the EGFR; OSI-774 (erlotinib/Tarceva; Genentech/OSI/Roch) and ZD1839 (gefitinib/Iressa; AstraZeneca), two small molecule EGFR-selective inhibitors of tyrosine kinase enzymatic activity, which prevent EGFR autophosphorylation and activation. Iressa is the first EGFR-targeting agent to be registered as an anticancer drug in Japan, in Australia and in the US for the third-line treatment of chemoresistant non-small cell lung cancer (NSCLC) patients. This review will focus on the preclinical background and on the results from the first series of clinical trials with these drugs. Furthermore, continuing clinical trials and a series of open clinical issues for the development of optimal strategies of using EGFR-targeting agents will be discussed. |
| Handle: | http://hdl.handle.net/11562/346936 |
| Appare nelle tipologie: | 01.01 Articolo in Rivista |
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