Genetic predictors of MEK-dependence in non-small cell lung cancer

作者: Christine A. Pratilas , Aphrothiti J. Hanrahan , Ensar Halilovic , Yogindra Persaud , Junichi Soh

DOI: 10.1158/0008-5472.CAN-08-2223

关键词:

摘要: Hyperactivated extracellular signal-regulated kinase (ERK) signaling is common in human cancer and often the result of activating mutations BRAF, RAS, upstream receptor tyrosine kinases. To characterize mitogen-activated protein kinase/ERK (MEK)/ERK dependence lung cancers harboring BRAF domain mutations, we screened a large panel cell lines (n = 87) tumors 916) for mutations. We found that non-small (NSCLC) cells with both V600E non-V600E were selectively sensitive to MEK inhibition compared those epidermal growth factor (EGFR), KRAS, or ALK ROS fusions. Supporting its classification as "driver" mutation which it expressed, (V600E)BRAF NSCLC led substantial induction apoptosis, comparable seen EGFR mutant models. Despite high basal ERK phosphorylation, uniformly resistant inhibition. Conversely, These data, together nonoverlapping pattern cancer, suggest these lesions define distinct clinical entities whose treatment should be guided by prospective real-time genotyping. facilitate such an effort, developed mass spectrometry-based genotyping method detection hotspot EGFR. Using this assay, confirmed can identified minority patients harbor have profile

参考文章(42)
Makoto Suzuki, Hisayuki Shigematsu, Toshihiko Iizasa, Kenzo Hiroshima, Yukio Nakatani, John D. Minna, Adi F. Gazdar, Takehiko Fujisawa, Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer. ,vol. 106, pp. 2200- 2207 ,(2006) , 10.1002/CNCR.21853
David A. Tuveson, Sunil R. Hingorani, Michael A. Jacobetz, Gavin P. Robertson, Meenhard Herlyn, Suppression of BRAFV599E in Human Melanoma Abrogates Transformation Cancer Research. ,vol. 63, pp. 5198- 5202 ,(2003)
C.-H. Yun, K. E. Mengwasser, A. V. Toms, M. S. Woo, H. Greulich, K.-K. Wong, M. Meyerson, M. J. Eck, The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP Proceedings of the National Academy of Sciences of the United States of America. ,vol. 105, pp. 2070- 2075 ,(2008) , 10.1073/PNAS.0709662105
J Guillermo Paez, Pasi A Janne, Jeffrey C Lee, Sean Tracy, Heidi Greulich, Stacey Gabriel, Paula Herman, Frederic J Kaye, Neal Lindeman, Titus J Boggon, Katsuhiko Naoki, Hidefumi Sasaki, Yoshitaka Fujii, Michael J Eck, William R Sellers, Bruce E Johnson, Matthew Meyerson, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. ,vol. 304, pp. 1497- 1500 ,(2004) , 10.1126/SCIENCE.1099314
Helen Davies, Graham R. Bignell, Charles Cox, Philip Stephens, Sarah Edkins, Sheila Clegg, Jon Teague, Hayley Woffendin, Mathew J. Garnett, William Bottomley, Neil Davis, Ed Dicks, Rebecca Ewing, Yvonne Floyd, Kristian Gray, Sarah Hall, Rachel Hawes, Jaime Hughes, Vivian Kosmidou, Andrew Menzies, Catherine Mould, Adrian Parker, Claire Stevens, Stephen Watt, Steven Hooper, Rebecca Wilson, Hiran Jayatilake, Barry A. Gusterson, Colin Cooper, Janet Shipley, Darren Hargrave, Katherine Pritchard-Jones, Norman Maitland, Georgia Chenevix-Trench, Gregory J. Riggins, Darell D. Bigner, Giuseppe Palmieri, Antonio Cossu, Adrienne Flanagan, Andrew Nicholson, Judy W. C. Ho, Suet Y. Leung, Siu T. Yuen, Barbara L. Weber, Hilliard F. Seigler, Timothy L. Darrow, Hugh Paterson, Richard Marais, Christopher J. Marshall, Richard Wooster, Michael R. Stratton, P. Andrew Futreal, Mutations of the BRAF gene in human cancer Nature. ,vol. 417, pp. 949- 954 ,(2002) , 10.1038/NATURE00766
Astrid Lièvre, Jean-Baptiste Bachet, Delphine Le Corre, Valérie Boige, Bruno Landi, Jean-François Emile, Jean-François Côté, Gorana Tomasic, Christophe Penna, Michel Ducreux, Philippe Rougier, Frédérique Penault-Llorca, Pierre Laurent-Puig, KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer Cancer Research. ,vol. 66, pp. 3992- 3995 ,(2006) , 10.1158/0008-5472.CAN-06-0191
Masaharu Nomura, Hisayuki Shigematsu, Lin Li, Makoto Suzuki, Takao Takahashi, Pila Estess, Mark Siegelman, Ziding Feng, Harubumi Kato, Antonio Marchetti, Jerry W Shay, Margaret R Spitz, Ignacio I Wistuba, John D Minna, Adi F Gazdar, Polymorphisms, Mutations, and Amplification of the EGFR Gene in Non-Small Cell Lung Cancers PLOS Medicine. ,vol. 4, pp. 715- 727 ,(2007) , 10.1371/JOURNAL.PMED.0040125
Klarisa Rikova, Ailan Guo, Qingfu Zeng, Anthony Possemato, Jian Yu, Herbert Haack, Julie Nardone, Kimberly Lee, Cynthia Reeves, Yu Li, Yerong Hu, Zhiping Tan, Matthew Stokes, Laura Sullivan, Jeffrey Mitchell, Randy Wetzel, Joan MacNeill, Jian Min Ren, Jin Yuan, Corey E. Bakalarski, Judit Villen, Jon M. Kornhauser, Bradley Smith, Daiqiang Li, Xinmin Zhou, Steven P. Gygi, Ting-Lei Gu, Roberto D. Polakiewicz, John Rush, Michael J. Comb, Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer Cell. ,vol. 131, pp. 1190- 1203 ,(2007) , 10.1016/J.CELL.2007.11.025
Matthew Meyerson, David J. Sugarbaker, William G. Richards, Tzu Hsiu Chen, Katsuhiko Naoki, Missense mutations of the BRAF gene in human lung adenocarcinoma Cancer Research. ,vol. 62, pp. 7001- 7003 ,(2002)