The role of EGFR inhibitors in nonsmall cell lung cancer

被引:94
作者
Ciardiello, F
De Vita, F
Orditura, M
Tortora, G
机构
[1] Univ Naples 2, Dipartimento Med Chirurg Internist Clin & Sperime, Cattedra Oncol Med, I-80131 Naples, Italy
[2] Univ Naples Federico II, Dip Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, Naples, Italy
关键词
nonsmall cell lung cancer; autocrine cancer cell growth; growth factor receptors; signal transcluction; monoclonal antibodies; small-molecule tyrosine kinase inhibitors;
D O I
10.1097/00001622-200403000-00008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review The epidermal growth factor receptor is a cell membrane receptor that plays a key role in cancer development and progression. Ligand-activated epidermal growth factor receptor-dependent signaling is involved in cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Targeting the epidermal growth factor receptor represents a promising molecular approach in cancer treatment. Several antiepidermal growth factor receptor agents are in clinical development. This review focuses on the available clinical data on epidermal growth factor receptor-targeting drugs in the treatment of nonsmall cell lung cancer. Recent findings Three drugs are currently in phase 2 and phase 3 development as single agents or in combination with other anticancer therapies in nonsmall cell lung cancer patients: cetuximab (Erbitux), a chimeric human-mouse monoclonal IgG1 antibody that blocks ligand binding and functional epidermal growth factor receptor activation; and erlotinib (Tarceva) and gefitinib (Iressa), two orally bioavailable, small-molecule epidermal growth factor receptor inhibitors of tyrosine kinase enzymatic activity that prevent epidermal growth factor receptor autophosphorylation and activation. Single-agent gefitinib treatment has determined a 10 to 20% response rate and a 30 to 50% symptom improvement in previously treated, chemotherapy-refractory advanced nonsmall cell lung cancer patients. Gefitinib has been the first epidermal growth factor receptor-targeting agent to be registered as an anticancer drug in several countries, including Japan, Australia, and the United States, for the third-line treatment of chemoresistant nonsmall cell lung cancer patients. Summary Antiepidermal growth factor receptor has shown promising antitumor activity in nonsmall cell lung cancer patients with a mild toxicity profile. However, a series of important clinical issues such as selection of potentially responsive patients and optimal combination with conventional anticancer treatments needs to be addressed to use these drugs better in lung cancer.
引用
收藏
页码:130 / 135
页数:6
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