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Your search keyword '"Rejto, Paul A."' showing total 5 results
Start Over Author "Rejto, Paul A." Journal plos one
5 results on '"Rejto, Paul A."'

2. Correction: A Novel SND1-BRAF Fusion Confers Resistance to c-Met Inhibitor PF-04217903 in GTL16 Cells though MAPK Activation

Author

Lee, Nathan V., primary, Lira, Maruja E., additional, Pavlicek, Adam, additional, Ye, Jingjing, additional, Buckman, Dana, additional, Bagrodia, Shubha, additional, Srinivasa, Sreesha P., additional, Zhao, Yongjun, additional, Aparicio, Samuel, additional, Rejto, Paul A., additional, Christensen, James G., additional, and Ching, Keith A., additional

Published
2012
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3. A Comprehensive Characterization of Genome-Wide Copy Number Aberrations in Colorectal Cancer Reveals Novel Oncogenes and Patterns of Alterations

Author

Xie, Tao, primary, d’ Ario, Giovanni, additional, Lamb, John R., additional, Martin, Eric, additional, Wang, Kai, additional, Tejpar, Sabine, additional, Delorenzi, Mauro, additional, Bosman, Fred T., additional, Roth, Arnaud D., additional, Yan, Pu, additional, Bougel, Stephanie, additional, Di Narzo, Antonio Fabio, additional, Popovici, Vlad, additional, Budinská, Eva, additional, Mao, Mao, additional, Weinrich, Scott L., additional, Rejto, Paul A., additional, and Hodgson, J. Graeme, additional

Published
2012
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4. A Novel SND1-BRAF Fusion Confers Resistance to c-Met Inhibitor PF-04217903 in GTL16 Cells though MAPK Activation

Author

Lee, Nathan V., primary, Lira, Maruja E., additional, Pavlicek, Adam, additional, Ye, Jingjing, additional, Buckman, Dana, additional, Bagrodia, Shubha, additional, Srinivasa, Sreesha P., additional, Zhao, Yongjun, additional, Aparicio, Samuel, additional, Rejto, Paul A., additional, Christensen, James G., additional, and Ching, Keith A., additional

Published
2012
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5. A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation.

Author

Lee NV, Lira ME, Pavlicek A, Ye J, Buckman D, Bagrodia S, Srinivasa SP, Zhao Y, Aparicio S, Rejto PA, Christensen JG, and Ching KA

Subjects
Cell Line, Tumor, Drug Resistance, Neoplasm, Endonucleases, Humans, Nuclear Proteins genetics, Proto-Oncogene Proteins B-raf genetics, Recombinant Fusion Proteins genetics, Mitogen-Activated Protein Kinases metabolism, Nuclear Proteins metabolism, Proto-Oncogene Proteins B-raf metabolism, Proto-Oncogene Proteins c-met antagonists & inhibitors, Pyrazines pharmacology, Recombinant Fusion Proteins metabolism, Triazoles pharmacology
Abstract

Targeting cancers with amplified or abnormally activated c-Met (hepatocyte growth factor receptor) may have therapeutic benefit based on nonclinical and emerging clinical findings. However, the eventual emergence of drug resistant tumors motivates the pre-emptive identification of potential mechanisms of clinical resistance. We rendered a MET amplified gastric cancer cell line, GTL16, resistant to c-Met inhibition with prolonged exposure to a c-Met inhibitor, PF-04217903 (METi). Characterization of surviving cells identified an amplified chromosomal rearrangement between 7q32 and 7q34 which overexpresses a constitutively active SND1-BRAF fusion protein. In the resistant clones, hyperactivation of the downstream MAPK pathway via SND1-BRAF conferred resistance to c-Met receptor tyrosine kinase inhibition. Combination treatment with METi and a RAF inhibitor, PF-04880594 (RAFi) inhibited ERK activation and circumvented resistance to either single agent. Alternatively, treatment with a MEK inhibitor, PD-0325901 (MEKi) alone effectively blocked ERK phosphorylation and inhibited cell growth. Our results suggest that combination of a c-Met tyrosine kinase inhibitor with a BRAF or a MEK inhibitor may be effective in treating resistant tumors that use activated BRAF to escape suppression of c-Met signaling.

Published
2012
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