Abstract
Clinical tools to accurately describe, evaluate, and predict an individual’s response to cancer therapy are a field-wide priority; in many advanced cancers, only 10–20% of individuals will have a clinical benefit from therapy, yet we treat the entire population. Furthermore, many therapies are initially effective, but lose effectiveness over time. Here we describe methods to derive in vitro models of resistance to EGFR tyrosine kinase inhibitors. We additionally describe approaches to characterize possible mechanisms of resistance by genomic and transcriptomic approaches.
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References
Scaltriti, M., and Baselga, J. (2006) The epidermal growth factor receptor pathway: a model for targeted therapy. Clin. Cancer Res. 12, 5268–5272.
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., Louis, D. N., Christiani, D. C., Settleman, J., and Haber, D. A. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139.
Choi, S. H., Mendrola, J. M., and Lemmon, M. A. (2007) EGF-independent activation of cell-surface EGF receptors harboring mutations found in gefitinib-sensitive lung cancer. Oncogene 26, 1567–1576.
Kumar, A., Petri, E. T., Halmos, B., and Boggon, T. J. (2008) Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J. Clin. Oncol. 26, 1742–1751.
Shigematsu, H., and Gazdar, A. F. (2006) Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int. J. Cancer 118, 257–262.
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C. M., Zhao, X., Christensen, J., Kosaka, T., Holmes, A. J., Rogers, A. M., Cappuzzo, F., Mok, T., Lee, C., Johnson, B. E., Cantley, L. C., and Janne, P. A. (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039–1043.
Jiang, N., Leach, L. J., Hu, X., Potokina, E., Jia, T., Druka, A., Waugh, R., Kearsey, M. J., and Luo, Z. W. (2008) Methods for evaluating gene expression from Affymetrix microarray datasets. BMC Bioinformatics 9, 284.
Kwak, E. L., Sordella, R., Bell, D. W., Godin-Heymann, N., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Driscoll, D. R., Fidias, P., Lynch, T. J., Rabindran, S. K., McGinnis, J. P., Wissner, A., Sharma, S. V., Isselbacher, K. J., Settleman, J., and Haber, D. A. (2005) Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc. Natl. Acad. Sci. USA 102, 7665–7670.
Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., and Varmus, H. (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2, e73.
Engelman, J. A., Mukohara, T., Zejnullahu, K., Lifshits, E., Borras, A. M., Gale, C. M., Naumov, G. N., Yeap, B. Y., Jarrell, E., Sun, J., Tracy, S., Zhao, X., Heymach, J. V., Johnson, B. E., Cantley, L. C., and Janne, P. A. (2006) Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer. J. Clin. Invest. 116, 2695–2706.
Oleykowski, C. A., Bronson Mullins, C. R., Godwin, A. K., and Yeung, A. T. (1998) Mutation detection using a novel plant endonuclease. Nucleic Acids Res. 26, 4597–4602.
Qiu, P., Shandilya, H., D’Alessio, J. M., O’Connor, K., Durocher, J., and Gerard, G. F. (2004) Mutation detection using Surveyor nuclease. Biotechniques 36, 702–707.
Janne, P. A., Borras, A. M., Kuang, Y., Rogers, A. M., Joshi, V. A., Liyanage, H., Lindeman, N., Lee, J. C., Halmos, B., Maher, E. A., Distel, R. J., Meyerson, M., and Johnson, B. E. (2006) A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin. Cancer Res. 12, 751–758.
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Kani, K., Sordella, R., Mallick, P. (2012). Investigation of Acquired Resistance to EGFR-Targeted Therapies in Lung Cancer Using cDNA Microarrays. In: Kuster, B. (eds) Kinase Inhibitors. Methods in Molecular Biology, vol 795. Humana Press. https://doi.org/10.1007/978-1-61779-337-0_16
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DOI: https://doi.org/10.1007/978-1-61779-337-0_16
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