The Effects of Cetuximab Alone and in Combination With Radiation and/or Chemotherapy in Lung Cancer

作者：David Raben, Barb Helfrich, Daniel C. F. Chan, Fortunato Ciardiello, Limin Zhao, Wilbur A. Franklin, Anna E. Barón, Chan Zeng, Tim K. Johnson, Paul A. Bunn · 发表于：Clinical Cancer Research · 年份：2005 · DOI：10.1158/1078-0432.795.11.2 · 被引用次数：244 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Cancer Immunotherapy and Biomarkers

PURPOSE: The epidermal growth factor receptor (EGFR) overexpressed in approximately 80% of non-small cell lung cancers (NSCLC) is a target for novel therapeutics. Concurrent chemoradiation is the current standard of care for treatment of patients with locally advanced NSCLC. However, < 20% of patients remain disease-free at 5 years despite this aggressive treatment. Cetuximab is a humanized monoclonal antibody that recognizes the human EGFR, and in previous studies, inhibited the growth of EGFR-expressing human cancer cell lines. In this report, we investigated the cellular and molecular effects of cetuximab alone and in combination with radiation and/or chemotherapy in human NSCLC cell lines with varying levels of EGFR overexpression in vitro and in vivo. EXPERIMENTAL DESIGN: We evaluated the EGFR status of a panel of human NSCLC cancer cell lines by immunohistochemistry and flow cytometry. We then evaluated cetuximab effects on growth, cell cycle distribution, and downstream intracellular signaling molecules in this panel of NSCLC cancer cell lines. NSCLC cell lines were treated with cetuximab alone or in combination with radiation, chemotherapy, or chemoradiation to determine the cooperative effects of cetuximab both in vitro and in vivo in athymic nude mice bearing NSCLC xenografts. RESULTS: Cetuximab alone inhibited the in vitro growth of some but not all EGFR-expressing NSCLC cell lines in a dose-dependent manner. Flow cytometric analysis of cell cycle distribution afte...