1. Sequence-dependent antiproliferative effects of cytotoxic drugs and epidermal growth factor receptor inhibitors
- Author
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Maria Pia Morelli, Giampaolo Tortora, Michele Orditura, Tina Cascone, Fortunato Ciardiello, Teresa Troiani, S. G. Eckhardt, F. De Vita, G. Laus, Stefano Pepe, M. P., Morelli, T., Cascone, Troiani, Teresa, F., De Vita, M., Orditura, Laus, Gianluca, S. G., Eckhardt, Pepe, Stefano, Tortora, Giampaolo, F. C. i. a. r. d. i. e. l. l., O., Morelli, Mp, Cascone, T, DE VITA, Ferdinando, Orditura, Michele, Laus, G, Eckhardt, Sg, Pepe, S, Tortora, G, and Ciardiello, Fortunato
- Subjects
Cancer therapy ,Esophageal Neoplasms ,Organoplatinum Compounds ,Cetuximab ,Docetaxel ,KYSE30 cell ,Pharmacology ,ZD6474 ,Carboplatin ,chemistry.chemical_compound ,Piperidines ,Growth factor receptor inhibitor ,Epidermal growth factor receptor ,cell cycle distribution ,EGFR inhibitors ,biology ,Cell Cycle ,Antibodies, Monoclonal ,Gefitinib ,Hematology ,ErbB Receptors ,Oxaliplatin ,Oncology ,cytotoxic drugs ,Carcinoma, Squamous Cell ,Taxoids ,A431 cells ,medicine.drug ,Paclitaxel ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,platinum derivative ,Cell Line, Tumor ,medicine ,combined treatment ,Humans ,cell growth inhibition ,Cisplatin ,Dose-Response Relationship, Drug ,business.industry ,apoptosi ,flow cytometry ,chemistry ,Quinazolines ,biology.protein ,business - Abstract
BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are in clinical development in cancer treatment. Preclinical studies have shown potential antitumor efficacy of these agents in combination with chemotherapy or with radiotherapy. However, controversial results have been obtained in different clinical trials. MATERIALS AND METHODS: The effects on proliferation, cell cycle distribution and induction of apoptosis of three different anti-EGFR agents (gefitinib, ZD6474, cetuximab) were evaluated in different sequences of combination with either a platinum derivative (cisplatin, carboplatin, oxaliplatin) or a taxane (docetaxel, paclitaxel) in KYSE30 cells, a model of a human cancer cell line with a functional EGFR autocrine pathway. RESULTS: The combination of a cytotoxic drug with an EGFR inhibitor caused different antiproliferative effects on KYSE30 cancer cells depending on the treatment schedule. An antagonistic effect was observed when treatment with each EGFR inhibitor was done before chemotherapy. In contrast, a synergistic antiproliferative activity was obtained when chemotherapy was followed by treatment with EGFR antagonists. This effect was accompanied by potentiation of apoptosis and arrest of the surviving cancer cells in the G(2)/M phases of the cell cycle. CONCLUSIONS: This study provides a rationale for the evaluation of a potentially synergistic sequence of cytotoxic drugs and EGFR inhibitors in a clinical setting.
- Published
- 2005