The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Genetic Predictors of MEK Dependence in Non–Small Cell Lung Cancer
Open accessAbstract
Hyperactivated extracellular signal-regulated kinase (ERK) signaling is common in human cancer and is often the result of activating mutations in BRAF, RAS, and upstream receptor tyrosine kinases. To characterize the mitogen-activated protein kinase/ERK kinase (MEK)/ERK dependence of lung cancers harboring BRAF kinase domain mutations, we screened a large panel of human lung cancer cell lines (n = 87) and tumors (n = 916) for BRAF mutations. We found that non–small cell lung cancers (NSCLC) cells with both V600E and non-V600E BRAF mutations were selectively sensitive to MEK inhibition compared with those harboring mutations in epidermal growth factor receptor (EGFR), KRAS, or ALK and ROS kinase fusions. Supporting its classification as a “driver” mutation in the cells in which it is expressed, MEK inhibition in V600EBRAF NSCLC cells led to substantial induction of apoptosis, comparable with that seen with EGFR kinase inhibition in EGFR mutant NSCLC models. Despite high basal ERK phosphorylation, EGFR mutant cells were uniformly resistant to MEK inhibition. Conversely, BRAF mutant cell lines were resistant to EGFR inhibition. These data, together with the nonoverlapping pattern of EGFR and BRAF mutations in human lung cancer, suggest that these lesions define distinct clinical entities whose treatment should be guided by prospective real-time genotyping. To facilitate such an effort, we developed a mass spectrometry-based genotyping method for the detection of hotspot mutations in BRAF, KRAS, and EGFR. Using this assay, we confirmed that BRAF mutations can be identified in a minority of NSCLC tumors and that patients whose tumors harbor BRAF mutations have a distinct clinical profile compared with those whose tumors harbor kinase domain mutations in EGFR. [Cancer Res 2008;68(22):9375–83]
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Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338
Self-citationPao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527 · cited 3×
“Treatment of H3255 (EGFR) cells with gefitinib resulted in profound induction of apoptosis as measured by FACS, whereas H1975 cells were resistant to gefitinib due to the presence of the T790M mutation (7).”
BackgroundSelf-citationMechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF
Wan, P. T. C., Garnett, M. J., Roe, S. M., Lee, S., Niculescu-Duvaz, D., Good, V. M., Project, C. G., Jones, C. M., Marshall, C. J., Springer, C. J., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00215-6 · Cited by 2,808
Shigematsu, H., Lin, L., Takahashi, T., Nomura, M., Suzuki, M., Wistuba, I. I., Fong, K. M., Lee, H., Toyooka, S., Shimizu, N., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji055 · Cited by 2,377
Self-citationGlobal Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Lièvre, A., Bachet, J.-B., Le Corre, D., Boige, V., Landi, B., Emile, J.-F., Côté, J.-F., Tomasic, G., Penna, C., Ducreux, M., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0191 · Cited by 2,229
Cited by
Non-small cell lung cancer: current treatment and future advances
Zappa, C., & Mousa, S. A. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.06.07 · Cited by 1,944
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
Pao, W., & Chmielecki, J. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2947 · Cited by 1,083
“gov/drugdictionary/?CdrID=456780">PD0325901 but are resistant to EGFR inhibitio”
BackgroundSelf-citationMEK1 and MEK2 inhibitors and cancer therapy: the long and winding road
Caunt, C. J., Sale, M. J., Smith, P. D., & Cook, S. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4000 · Cited by 606
Negative feedback regulation of the ERK1/2 MAPK pathway
Lake, D., Corrêa, S. A. L., & Müller, J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2297-8 · Cited by 565
Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents
Sharma, S. V., Haber, D. A., & Settleman, J. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2820 · Cited by 586
Metadata
- Authors
- Pratilas, C. A., Hanrahan, A. J., Halilovic, E., Persaud, Y., Soh, J., Chitale, D., Shigematsu, H., Yamamoto, H., Sawai, A., Janakiraman, M., Taylor, B. S., Pao, W., Toyooka, S., Ladanyi, M., Gazdar, A., Rosen, N., & Solit, D. B.
- Venue
- Cancer Research
- Published
- 2008-11-14
- Volume
- 68
- Issue
- 22
- Pages
- 9375-9383
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2123611729
- Cited by
- 255
- References
- 41
- FWCI
- 20.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pratilas, C. A., Hanrahan, A. J., Halilovic, E., Persaud, Y., Soh, J., Chitale, D., Shigematsu, H., Yamamoto, H., Sawai, A., Janakiraman, M., Taylor, B. S., Pao, W., Toyooka, S., Ladanyi, M., Gazdar, A., Rosen, N., & Solit, D. B. (2008). Genetic Predictors of MEK Dependence in Non–Small Cell Lung Cancer. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-2223
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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