کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3990476 1258738 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Preclinical Rationale for Use of the Clinically Available Multitargeted Tyrosine Kinase Inhibitor Crizotinib in ROS1-Translocated Lung Cancer
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
Preclinical Rationale for Use of the Clinically Available Multitargeted Tyrosine Kinase Inhibitor Crizotinib in ROS1-Translocated Lung Cancer
چکیده انگلیسی

Introduction:Most clinically available small-molecule kinase inhibitors are multi-targeted and can inhibit multiple kinases. Our driving hypothesis was that one of these multi-targeted tyrosine kinase inhibitors (TKIs) would have antiproliferative activity against ROS1 translocated non–small-cell lung cancer (NSCLC).Methods:We selected NSCLC cell lines—A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)—to evaluate the antiproliferative effects of submicromolar concentrations of the multitargeted TKIs imatinib, sorafenib, erlotinib, and crizotinib.Results:Imatinib and sorafenib were unable to significantly inhibit proliferation of the aforementioned cell lines. Erlotinib only inhibited EGFR mutated NCI-H3255, as expected. Crizotinib displayed dose-dependent inhibition of anaplastic lymphoma kinase translocated NCI-H3122 and also ROS1-translocated HCC78. The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis.Conclusions:The ROS1-translocated HCC78 cell line was sensitive to inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib. Preclinical data supports the clinical development of crizotinib for ROS1-translocated NSCLC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Thoracic Oncology - Volume 7, Issue 7, July 2012, Pages 1086–1090
نویسندگان
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