signatures of drug sensitivity in nonsmall cell lung cancer签名nonsmall细胞肺癌的药物敏感性.pdfVIP

Hindawi Publishing Corporation International Journal of Proteomics Volume 2011, Article ID 215496, 13 pages doi:10.1155/2011/215496 Research Article Signatures of Drug Sensitivity in Nonsmall Cell Lung Cancer Hua C. Gong,1 Sean Wang,1 Gary Mayer,1 Guoan Chen,2 Glen Leesman,1 Sharat Singh,1 and David G. Beer3 1 Department of Research and Development, Prometheus Inc. 9410, Carroll Park Drive, San Diego, CA 92121, USA 2 Department of Surgery, School of Medicine, University of Michigan, 6304 Cancer Center, Ann Arbor, MI 48109, USA 3 Cancer Center, University of Michigan, Room 6304, Ann Arbor, MI 48109, USA Correspondence should be addressed to Sharat Singh, ssingh@ and David G. Beer, dgbeer@ Received 27 April 2011; Accepted 1 June 2011 Academic Editor: David E. Misek Copyright © 2011 Hua C. Gong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We profiled receptor tyrosine kinase pathway activation and key gene mutations in eight human lung tumor cell lines and 50 human lung tumor tissue samples to define molecular pathways. A panel of eight kinase inhibitors was used to determine whether blocking pathway activation affected the tumor cell growth. The HER1 pathway in HER1 mutant cell lines HCC827 and H1975 were found to be highly activated and sensitive to HER1 inhibition. H1993 is a c-MET amplified cell line showing c-MET and HER1 pathway activation and responsiveness to c-MET inhibitor treatment. IGF-1R pathway activated H358 and A549 cells are sensitive to IGF-1R inhibition. The downstream PI3K inhibitor, BEZ-235, effectively inhibited tumor cell growth in most of the cell