Table of Contents
International Journal of Proteomics
Volume 2011 (2011), Article ID 215496, 13 pages
http://dx.doi.org/10.1155/2011/215496
Research Article

Signatures of Drug Sensitivity in Nonsmall Cell Lung Cancer

1Department of Research and Development, Prometheus Inc. 9410, Carroll Park Drive, San Diego, CA 92121, USA
2Department of Surgery, School of Medicine, University of Michigan, 6304 Cancer Center, Ann Arbor, MI 48109, USA
3Cancer Center, University of Michigan, Room 6304, Ann Arbor, MI 48109, USA

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.

Abstract

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 lines tested, except the H1993 and H1650 cells, while the MEK inhibitor PD-325901 was effective in blocking the growth of KRAS mutated cell line H1734 but not H358, A549 and H460. Hierarchical clustering of primary tumor samples with the corresponding tumor cell lines based on their pathway signatures revealed similar profiles for HER1, c-MET and IGF-1R pathway activation and predict potential treatment options for the primary tumors based on the tumor cell lines response to the panel of kinase inhibitors.