Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization

Cho, Jeonghee; Chen, Liang; Sangji, Naveen; Okabe, Takafumi; Yonesaka, Kimio; Francis, Joshua M.; Flavin, Richard J.; Johnson, William; Kwon, Jihyun; Yu, Soyoung; Greulich, Heidi; Johnson, Bruce E.; Eck, Michael J.; Jänne, Pasi A.; Wong, Kwok-Kin; Meyerson, Matthew

doi:10.1158/0008-5472.can-13-1145

Cited by 117Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchProtein Kinase Regulation and GTPase Signaling

Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization

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Cho, Jeonghee, Chen, Liang, Sangji, Naveen, Okabe, Takafumi, Yonesaka, Kimio, Francis, Joshua M., Flavin, Richard J., Johnson, William +8 more·2013·Cancer Research

DOI 10.1158/0008-5472.can-13-1145PMC PMC3903789

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Abstract

Kinase domain mutations of the EGF receptor (EGFR) are common oncogenic events in lung adenocarcinoma. Here, we explore the dependency upon asymmetric dimerization of the kinase domain for activation of lung cancer-derived EGFR mutants. We show that whereas wild-type EGFR and the L858R mutant require dimerization for activation and oncogenic transformation, the exon 19 deletion, exon 20 insertion, and L858R/T790M EGFR mutants do not require dimerization. In addition, treatment with the monoclonal antibody, cetuximab, shrinks mouse lung tumors induced by the dimerization-dependent L858R mutant, but exerts only a modest effect on tumors driven by dimerization-independent EGFR mutants. These data imply that different EGFR mutants show differential requirements for dimerization and that disruption of dimerization may be among the antitumor mechanisms of cetuximab.

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Emerging clinical data show that C797S is detected in approximately 40% of EGFR mutant NSCLC patients with T790M who develop acquired resistance to AZD9291.
“Emerging clinical data reveal that the C797S mutation is detected in ~ 40% of EGFR mutant NSCLC patients with T790M who develop acquired resistance to AZD9291(36).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [36]

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Zhang, X., Gureasko, J., Shen, K., Cole, P. A., & Kuriyan, J. (2006) · Cell · doi:10.1016/j.cell.2006.05.013 · Cited by 1,650 · see citing works
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Yun, C.-H., Boggon, T. J., Li, Y., Woo, M. S., Greulich, H., Meyerson, M., & Eck, M. J. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.12.017 · Cited by 1,192 · cited 1× · see citing works
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Li, S., Schmitz, K. R., Jeffrey, P. D., Wiltzius, J. J. W., Kussie, P. H., & Ferguson, K. M. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.03.003 · Cited by 1,117 · see citing works
Novel mutant-selective EGFR kinase inhibitors against EGFR T790M
Zhou, W., Ercan, D., Chen, L., Yun, C.-H., Li, D., Capelletti, M., Cortot, A. B., Chirieac, L., Iacob, R. E., Padera, R., et al. (2009) · Nature · doi:10.1038/nature08622 · Cited by 1,013 · see citing works
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Self-citation
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Self-citation
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Sos, M. L., Koker, M., Weir, B. A., Heynck, S., Rabinovsky, R., Zander, T., Seeger, J. M., Weiss, J., Fischer, F., Frommolt, P., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4055 · Cited by 504 · see citing works
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Ji, H., Li, D., Chen, L., Shimamura, T., Kobayashi, S., McNamara, K., Mahmood, U., Mitchell, A., Sun, Y., Al-Hashem, R., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.022 · Cited by 462 · see citing works
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Self-citation
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Ferguson, K. M. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125829 · Cited by 368 · see citing works
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Shan, Y., Eastwood, M. P., Zhang, X., Kim, E. T., Arkhipov, A. S., Dror, R. O., Jumper, J., Kuriyan, J., & Shaw, D. E. (2012) · Cell · doi:10.1016/j.cell.2012.02.063 · Cited by 360 · see citing works
Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface
Zhang, X., Pickin, K. A., Bose, R., Jura, N., Cole, P. A., & Kuriyan, J. (2007) · Nature · doi:10.1038/nature05998 · Cited by 357 · see citing works
Somatic Mutations ofEGFRin Colorectal Cancers and Glioblastomas
Barber, T. D., Vogelstein, B., Kinzler, K. W., & Velculescu, V. E. (2004) · New England Journal of Medicine · doi:10.1056/nejm200412303512724 · Cited by 314 · see citing works
Differential Effects of Gefitinib and Cetuximab on Non–small-cell Lung Cancers Bearing Epidermal Growth Factor Receptor Mutations
Mukohara, T., Engelman, J. A., Hanna, N. H., Yeap, B. Y., Kobayashi, S. S., Lindeman, N. I., Halmos, B., Pearlberg, J., Tsuchihashi, Z., Cantley, L. C., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji238 · Cited by 313 · see citing works
Self-citation
The epidermal growth factor receptor–tyrosine kinase: A promising therapeutic target in solid tumors
Ritter, C. A., & Arteaga, C. L. (2003) · Seminars in Oncology · doi:10.1053/sonc.2003.50027 · Cited by 312 · see citing works
Sensitivity to gefitinib (Iressa, ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the epidermal growth factor (EGF) receptor/extracellular signal-regulated kinase 1/2 and EGF receptor/Akt pathway for proliferation
Ono, M., Hirata, A., Kometani, T., Miyagawa, M., Ueda, S.-I., Kinoshita, H., Fujii, T., & Kuwano, M. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.465.3.4 · Cited by 305 · see citing works
Epidermal Growth Factor Receptor Dimerization and Activation Require Ligand-Induced Conformational Changes in the Dimer Interface
Dawson, J. P., Berger, M. B., Lin, C.-C., Schlessinger, J., Lemmon, M. A., & Ferguson, K. M. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.17.7734-7742.2005 · Cited by 298 · see citing works
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Jiang, J., Greulich, H. E., Janne, P. A., Sellers, W. R., Meyerson, M. M., & Griffin, J. D. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1829 · Cited by 188 · see citing works
Self-citation
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Yoshida, K., Yatabe, Y., Park, J. Y., Shimizu, J., Horio, Y., Matsuo, K., Kosaka, T., Mitsudomi, T., & Hida, T. (2007) · Journal of Thoracic Oncology · doi:10.1016/s1556-0864(15)30013-7 · Cited by 165 · see citing works
Mutations of the epidermal growth factor receptor in non-small cell lung cancer – Search and destroy
Chan, S. K., Gullick, W. J., & Hill, M. E. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.07.031 · Cited by 165 · see citing works
Activity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib.
Janjigian, Y. Y., Groen, H. J. M., Horn, L., Smit, E. F., Fu, Y., Wang, F., Shahidi, M., Denis, L. J., Pao, W. J., & Miller, V. A. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.7525 · Cited by 145 · see citing works
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Tsuchihashi, Z., Khambata‐Ford, S., Hanna, N. H., & Janne, P. A. (2005) · New England Journal of Medicine · doi:10.1056/nejm200507143530218 · Cited by 118 · see citing works
Tumor Growth Inhibition with Cetuximab and Chemotherapy in Non–Small Cell Lung Cancer Xenografts Expressing Wild-type and Mutated Epidermal Growth Factor Receptor
Steiner, P., Joynes, C. J., Bassi, R., Wang, S., Tonra, J. R., Hadari, Y. R., & Hicklin, D. J. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1887 · Cited by 113 · see citing works
Prospective Validation for Prediction of Gefitinib Sensitivity by Epidermal Growth Factor Receptor Gene Mutation in Patients with Non-Small Cell Lung Cancer
Yoshida, K., Yatabe, Y., Park, J. Y., et al. (2007) · Journal of Thoracic Oncology · doi:10.1097/01243894-200701000-00006 · Cited by 109 · see citing works
Mechanistic insights into the activation of oncogenic forms of EGF receptor
Wang, Z., Longo, P. A., Tarrant, M. K., Kim, K., Head, S. A., Leahy, D. J., & Cole, P. A. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2168 · Cited by 94 · see citing works
Epidermal Growth Factor Receptor (EGFR) Antibody Down-regulates Mutant Receptors and Inhibits Tumors Expressing EGFR Mutations
Pérez-Torres, M., Guix, M., González, A., & Arteaga, C. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607958200 · Cited by 89 · see citing works
Allele-dependent variation in the relative cellular potency of distinct EGFR inhibitors
Yuza, Y., Glatt, K. A., Jiang, J., Greulich, H., Minami, Y., Woo, M. S., Shimamura, T., Shapiro, G. I., Lee, J. C., Ji, H., et al. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.5.4003 · Cited by 88 · see citing works
Self-citation
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Sasaki, H., Endo, K., Takada, M., Kawahara, M., Kitahara, N., Tanaka, H., Okumura, M., Matsumura, A., Iuchi, K., Kawaguchi, T., et al. (2007) · Lung Cancer · doi:10.1016/j.lungcan.2007.06.024 · Cited by 84 · see citing works
Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) to Analyze the Disruption of EGFR/HER2 Dimers
Gaborit, N., Larbouret, C., Vallaghe, J., Peyrusson, F., Mollévi, C., Lopez‐Crapez, E., Azria, D., Chardès, T., Poul, M., Mathis, G., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.223503 · Cited by 80 · see citing works
Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed Therapies
Cho, J., Pastorino, S., Zeng, Q., Xu, X., Johnson, W. E., VandenBerg, S. R., Verhaak, R. G. W., Cherniack, A. D., Watanabe, H., Dutt, A., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0821 · Cited by 73 · see citing works
Self-citation
Pathology of small cell carcinoma of the lung
Zakowski, M. F. (2003) · Seminars in Oncology · doi:10.1053/sonc.2003.50015 · Cited by 60 · see citing works
Antibody-mediated EGF receptor blockade as an anticancer therapy: from the laboratory to the clinic
Mendelsohn, J. M. (2003) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-002-0354-7 · Cited by 58 · see citing works
Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non–small cell lung cancers
Doody, J. F., Wang, Y., Patel, S. N., Joynes, C. J., Lee, S. P., Gerlak, J., Rolser, R. L., Li, Y., Steiner, P., Bassi, R., et al. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0506 · Cited by 56 · see citing works
Modeling oncogene addiction using RNA interference
Rothenberg, S. M., Engelman, J. A., Le, S., Riese, D. J., Haber, D. A., & Settleman, J. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803217105 · Cited by 45 · see citing works
Phosphorylation of Tyrosine 992, 1068, and 1086 Is Required for Conformational Change of the Human Epidermal Growth Factor Receptor C-Terminal Tail
Bishayee, A., Beguinot, L., & Bishayee, S. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.3.525 · Cited by 35 · see citing works
Conformational dynamics of the EGFR kinase domain reveals structural features involved in activation
Papakyriakou, A., Vourloumis, D., Tzortzatou-Stathopoulou, F. F., & Karpusas, M. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22353 · Cited by 31 · see citing works
Phase I study of gefitinib, irinotecan, 5-fluorouracil and leucovorin in patients with metastatic colorectal cancer
Meyerhardt, J. A., Clark, J. W., Supko, J. G., Eder, J. P., Ogino, S., Stewart, C. F., D’Amato, F., Dancey, J. E., Enzinger, P. C., Zhu, A. X., et al. (2007) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-006-0411-6 · Cited by 26 · see citing works
Epidermal growth factor receptor lacking C‐terminal autophosphorylation sites retains signal transduction and high sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor
Maegawa, M., Arao, T., Yokote, H., MATSUMOTO, K. Y., Kudo, K., Tanaka, K., Kaneda, H., Fujita, Y., Ito, F., & Nishio, K. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2008.01071.x · Cited by 14 · see citing works

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Yasuda, H., Park, E., Yun, C.-H., Sng, N. J., Lucena-Araujo, A. R., Yeo, W.-L., Huberman, M. S., Cohen, D. W., Nakayama, S., Ishioka, K., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007205 · Cited by 571 · see citing works
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Transferrin receptor targeting chimeras for membrane protein degradation
Zhang, D., Duque-Jimenez, J., Facchinetti, F., Brixi, G., Rhee, K., Feng, W. W., Janne, P. A., & Zhou, X. X. (2024) · Nature · doi:10.1038/s41586-024-07947-3 · Cited by 205 · see citing works
An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer
To, C., Beyett, T. S., Jang, J., Feng, W. W., Bahcall, M., Haikala, H. M., Shin, B. H., Heppner, D. E., Rana, J. K., Leeper, B. A., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00351-8 · Cited by 168 · see citing works
Self-citation
EGFR Fusions as Novel Therapeutic Targets in Lung Cancer
Konduri, K., Gallant, J.-N., Chae, Y. K., Giles, F. J., Gitlitz, B. J., Gowen, K., Ichihara, E., Owonikoko, T. K., Peddareddigari, V., Ramalingam, S. S., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0075 · Cited by 144 · see citing works
Molecular Mechanisms and Targeted Therapies Including Immunotherapy for Non-Small Cell Lung Cancer
Nagano, T., TACHIHARA, M. Y., & Nishimura, Y. (2018) · Current Cancer Drug Targets · doi:10.2174/1568009619666181210114559 · Cited by 118 · see citing works
A Third Shot at EGFR: New Opportunities in Cancer Therapy
Guardiola, S., Varese, M., Sánchez‐Navarro, M., & Giralt, E. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.10.004 · Cited by 106 · see citing works
Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors
Wang, S., Song, Y., Yan, F., & Liu, D. (2016) · Frontiers of Medicine · doi:10.1007/s11684-016-0488-1 · Cited by 96 · see citing works
Enhanced dimerization drives ligand-independent activity of mutant epidermal growth factor receptor in lung cancer
Valley, C. C., Arndt‐Jovin, D. J., Karedla, N., Steinkamp, M. P., Chizhik, A. I., Hlavacek, W. S., Wilson, B. S., Lidke, K. A., & Lidke, D. S. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-05-0269 · Cited by 93 · see citing works
First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations
Okuma, Y., Kubota, K., Shimokawa, M., Hashimoto, K., Kawashima, Y., Sakamoto, T., Wakui, H., Murakami, S., Okishio, K., Hayashihara, K., et al. (2023) · JAMA Oncology · doi:10.1001/jamaoncol.2023.5013 · Cited by 93 · see citing works
Structure and mechanism of activity-based inhibition of the EGF receptor by Mig6
Park, E., Kim, N., Ficarro, S. B., Zhang, Y., Lee, B. I., Cho, A., Kim, K., Park, A. K.-J., Park, W., Murray, B. A., et al. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3074 · Cited by 85 · see citing works
Self-citation
Emerging Approaches to Overcome Acquired Drug Resistance Obstacles to Osimertinib in Non-Small-Cell Lung Cancer
Shaikh, M., Shinde, Y., Pawara, R. H., Noolvi, M. N., Surana, S. J., Ahmad, I., & Patel, H. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00876 · Cited by 81 · see citing works
BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Lim, S. M., Fujino, T., Kim, C., Lee, G., Lee, Y.-H., Kim, D., Ahn, J. S., Mitsudomi, T., Jin, T. J., & Lee, S.-Y. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-3901 · Cited by 86 · see citing works
Structure–function analysis of oncogenic EGFR Kinase Domain Duplication reveals insights into activation and a potential approach for therapeutic targeting
Du, Z., Brown, B. P., Kim, S., Ferguson, D. C., Pavlick, D. C., Jayakumaran, G., Benayed, R., Gallant, J., Zhang, Y., Yan, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21613-6 · Cited by 67 · see citing works
Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non–Small-Cell Lung Cancer: Final Results From SWOG S1403
Goldberg, S. B., Redman, M. W., Lilenbaum, R., Politi, K. A., Stinchcombe, T. E., Horn, L., Chen, E. H., Mashru, S. H., Gettinger, S. N., Melnick, M. A., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.01149 · Cited by 65 · see citing works
Altered conformational landscape and dimerization dependency underpins the activation of EGFR by α C– β 4 loop insertion mutations
Ruan, Z., & Kannan, N. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803152115 · Cited by 59 · see citing works
Resistance to EGFR inhibitors in non-small cell lung cancer: Clinical management and future perspectives
Tomasello, C., Baldessari, C., Napolitano, M., Orsi, G., Grizzi, G., Bertolini, F., Barbieri, F., & Cascinu, S. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.01.013 · Cited by 64 · see citing works
PIK3CA Pathway Mutations Predictive of Poor Response Following Standard Radiochemotherapy ± Cetuximab in Cervical Cancer Patients
de la Rochefordière, A., Kamal, M. T., Floquet, A., Thomas, L., Petrow, P. K., Petit, T., Pop, M., Fabbro, M., Kerr, C., Joly, F., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2368 · Cited by 55 · see citing works
Receptor tyrosine kinases in PI3K signaling: The therapeutic targets in cancer
Jiang, W., & Ji, M. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.03.006 · Cited by 53 · see citing works
New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?
Steen, N. V. D., Caparello, C., Rolfo, C. D., Pauwels, P., Peters, G. J., & Giovannetti, E. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s97644 · Cited by 52 · see citing works
Progression of EGFR-Mutant Lung Adenocarcinoma is Driven By Alveolar Macrophages
Wang, D.-H., Lee, H., Yoon, D. K., Berry, G. J., Wheeler, T. M., Sugarbaker, D. J., Kheradmand, F., Engleman, E. G., & Burt, B. M. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2597 · Cited by 51 · see citing works
Utility of the Ba/F3 cell system for exploring on‐target mechanisms of resistance to targeted therapies for lung cancer
Koga, T., Suda, K., & Mitsudomi, T. (2022) · Cancer Science · doi:10.1111/cas.15263 · Cited by 50 · see citing works
Mechanisms of resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors and therapeutic strategies in non-small cell lung cancer
Xu, J., Wang, J., & Zhang, S. (2017) · Oncotarget · doi:10.18632/oncotarget.21164 · Cited by 48 · see citing works
Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review
Karlsen, E., Kahler, S. L., Tefay, J., Joseph, S. R., & Simpson, F. (2021) · Cells · doi:10.3390/cells10051206 · Cited by 49 · see citing works
Structural basis of the effect of activating mutations on the EGF receptor
Galdadas, I., Carlino, L., Ward, R. A., Hughes, S. J., Haider, S. M., & Gervasio, F. L. (2021) · eLife · doi:10.7554/elife.65824 · Cited by 42 · see citing works
Transcription factor ZNF263 enhances EGFR-targeted therapeutic response and reduces residual disease in lung adenocarcinoma
Liang, J., Bi, G., Sui, Q., Zhao, G., Zhang, H., Bian, Y., Chen, Z., Huang, Y., Xi, J., Shi, Y., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113771 · Cited by 37 · see citing works
Combining three antibodies nullifies feedback-mediated resistance to erlotinib in lung cancer
Mancini, M., Gaborit, N., Lindzen, M., Salame, T. M., Dall’Ora, M., Sevilla-Sharon, M., Abdul‐Hai, A., Downward, J., & Yarden, Y. (2015) · Science Signaling · doi:10.1126/scisignal.aaa0725 · Cited by 38 · see citing works
Colorectal adenocarcinoma‐derived EGFR mutants are oncogenic and sensitive to EGFR‐targeted monoclonal antibodies, cetuximab and panitumumab
Kim, N., Cho, D., Kim, H., Kim, S., Cha, Y., Greulich, H. E., Bass, A. J., Cho, H., & Cho, J. (2019) · International Journal of Cancer · doi:10.1002/ijc.32499 · Cited by 38 · see citing works
Self-citation
Mechanistic Insights into R776H Mediated Activation of Epidermal Growth Factor Receptor Kinase
Ruan, Z., & Kannan, N. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00444 · Cited by 37 · see citing works
Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients
Umeda, Y., Hasegawa, Y., Otsuka, M., Ariki, S., Takamiya, R., Saito, A., Uehara, Y., Saijo, H., Kuronuma, K., Chiba, H., et al. (2017) · Oncogene · doi:10.1038/onc.2017.253 · Cited by 36 · see citing works
Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer
Brown, B. P., Zhang, Y., Kim, S., Finneran, P., Yan, Y., Du, Z., Kim, J., Hartzler, A. L., Lenoue-Newton, M. L., Smith, A. W., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2206588119 · Cited by 31 · see citing works
Epidermal Growth Factor Receptor Mutation as a Risk Factor for Recurrence in Lung Adenocarcinoma
Hayasaka, K., Shiono, S., Matsumura, Y., Yanagawa, N., Suzuki, H. Y., Abe, J., Sagawa, M., Sakurada, A., Katahira, M., Takahashi, S., et al. (2018) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2018.01.052 · Cited by 29 · see citing works
Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators
Marrocco, I., & Yarden, Y. (2023) · Cancers · doi:10.3390/cancers15205009 · Cited by 28 · see citing works
Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers
Kolesar, J., Peh, K. H., Thomas, L., Baburaj, G., Mukherjee, N., Kantamneni, R., Lewis, S. C., Pai, A., Udupa, K., Kumar, N. A. N., et al. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01534-8 · Cited by 30 · see citing works
Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab
Cho, J., Bass, A. J., Lawrence, M. S., Cibulskis, K., Cho, A., Lee, S.-N., Yamauchi, M., Wagle, N., Pochanard, P., Kim, N., et al. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-141 · Cited by 28 · see citing works
Self-citation
A narrative review of the role of common EGFR mutations in pathogenesis and treatment of non-small-cell lung carcinoma
Sharma, M., Basu, D. A., Nathany, S., Amrith, B. P., & Batra, U. (2022) · Cancer Research Statistics and Treatment · doi:10.4103/crst.crst_222_22 · Cited by 27 · see citing works
Resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer
Steen, N. V. D., Giovannetti, E., Carbone, D., Leonetti, A., Rolfo, C. D., & Peters, G. J. (2018) · Cancer Drug Resistance · doi:10.20517/cdr.2018.13 · Cited by 23 · see citing works
Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations
Takeyasu, Y., Yoshida, T., Masuda, K., Matsumoto, Y., Shinno, Y., Okuma, Y., Goto, Y., Horinouchi, H., Yamamoto, N., & Ohe, Y. (2024) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2024.100636 · Cited by 20 · see citing works
Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer
Romaniello, D., Morselli, A., & Marrocco, I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072957 · Cited by 20 · see citing works
Clinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer
Leone, G. M., Candido, S., Lavoro, A., Vivarelli, S., Gattuso, G., Călina, D. C., Libra, M., & Falzone, L. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041252 · Cited by 19 · see citing works
Allele-Specific Role of ERBB2 in the Oncogenic Function of EGFR L861Q in EGFR-Mutant Lung Cancers
Sato, H., Offin, M. D., Kubota, D., Yu, H. A., Wilhelm, C., Toyooka, S., Somwar, R., Kris, M. G., & Ladanyi, M. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.09.019 · Cited by 18 · see citing works
L858R emerges as a potential biomarker predicting response of lung cancer models to anti-EGFR antibodies: Comparison of osimertinib vs. cetuximab
Marrocco, I., Giri, S., Nieves, A. S., Gupta, N., Rudnitsky, A., Haga, Y., Romaniello, D., Sekar, A., Zerbib, M., Oren, R., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101142 · Cited by 17 · see citing works
Afatinib is especially effective against non-small cell lung cancer carrying an EGFR exon 19 deletion.
Banno, E., Togashi, Y., Kobayashi, Y., Hayashi, H., Mitsudomi, T., & Nishio, K. (2015) · PubMed · Cited by 17 · see citing works
A comprehensively revised strategy that improves the specific activity and long-term stability of clinically relevant 89 Zr-immuno-PET agents
Bhatt, N., Pandya, D. N., Rideout, S., Gage, H. D., Marini, F. C., & Wadas, T. J. (2018) · Dalton Transactions · doi:10.1039/c8dt01841c · Cited by 17 · see citing works
Treatment with immune checkpoint inhibitors after EGFR‐TKIs in EGFR ‐mutated lung cancer
Ito, T., Nagashima, H., Akiyama, M., Utsumi, Y., Sato, H., Chiba, S., Sugai, M., Ube, K., Mori, Y., Watanabe, K., et al. (2021) · Thoracic Cancer · doi:10.1111/1759-7714.14267 · Cited by 16 · see citing works
Constitutive asymmetric dimerization drives oncogenic activation of epidermal growth factor receptor carboxyl-terminal deletion mutants
Park, A. K.-J., Francis, J. M., Park, W., Park, J.-O., & Cho, J. (2015) · Oncotarget · doi:10.18632/oncotarget.3559 · Cited by 17 · see citing works
Self-citation
The complexity of EGFR exon 19 deletion and L858R mutant cells as assessed by proteomics, transcriptomics, and metabolomics
Ochi, N., Takeyama, M., Miyake, N., Fuchigami, M., Yamane, H., Fukazawa, T., Nagasaki, Y., Kawahara, T., Nakanishi, H., & Takigawa, N. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113503 · Cited by 17 · see citing works
AZD9291 overcomes T790 M-mediated resistance through degradation of EGFRL858R/T790M in non-small cell lung cancer cells
Ku, B. M., Bae, Y.-H., Koh, J., Sun, J., Lee, S.-H., Ahn, J. S., Park, K., & Ahn, M. (2016) · Investigational New Drugs · doi:10.1007/s10637-016-0350-y · Cited by 16 · see citing works
A Structural Insight Into Two Important ErbB Receptors (EGFR and HER2) and Their Relevance to Non‐Small Cell Lung Cancer
Topalan, E., Büyükgüngör, A., Çiğdem, M., Gura, S. F., Sever, B., Otsuka, M., Fujita, M., DeMi̇rci̇, H., & Ciftci, H. I. (2025) · Archiv der Pharmazie · doi:10.1002/ardp.202400992 · Cited by 16 · see citing works
From Rarity to Reality: Osimertinib’s Promising Horizon in Treating Uncommon EGFR Mutations in Non–Small Cell Lung Cancer
Fukuda, A., & Okuma, Y. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-4035 · Cited by 15 · see citing works
Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases
Tamura, K., Yoshida, T., Masuda, K., Matsumoto, Y., Shinno, Y., Okuma, Y., Goto, Y., Horinouchi, H., Yamamoto, N., & Ohe, Y. (2023) · ESMO Open · doi:10.1016/j.esmoop.2023.101594 · Cited by 14 · see citing works
Targeting inosine metabolism to enhance EGFR-targeted therapy in lung adenocarcinoma
Huang, X., Liang, J., Yi, Y., Zhu, J., Lin, H., Ren, S., Tao, C., Bi, G., Shan, G., Zeng, D., et al. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.218069 · Cited by 14 · see citing works
Impact of HER2 expression on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS study subset analysis
Ohashi, K., Ninomiya, K., Yoshioka, H., Bessho, A., Shibayama, T., Aoe, K., Ishikawa, N., Kozuki, T., Kawai, H., Kuyama, S., et al. (2020) · Lung Cancer · doi:10.1016/j.lungcan.2020.09.024 · Cited by 13 · see citing works
Comparison Between Second- and Third-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors as First-line Treatment in Patients With Non-small-cell Lung Cancer: A Retrospective Analysis
MITSUYA, S., Tsuruoka, K., Kanaoka, K., Funamoto, T., Tsuji, H., Matsunaga, N., Nakamura, T., Tamura, Y., Imanishi, M., IKEDA, S., et al. (2021) · Anticancer Research · doi:10.21873/anticanres.15331 · Cited by 13 · see citing works
Low plasma concentration of gefitinib in patients with EGFR exon 21 L858R point mutations shortens progression-free survival
Okuda, Y., Sato, K., Sudo, K., Hasegawa, Y., Asano, M., Miura, H., Takeda, M., Sano, M., Watanabe, H. A., Kobayashi, H., et al. (2017) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-017-3285-x · Cited by 12 · see citing works
Anti-EGFR aptamer exhibits direct anti-cancer effects in NSCLC cells harboring EGFR L858R mutations
Thomas, B. J., Awan, S. Z., Joshi, T., Daniëls, M. A., Porciani, D., & Burke, D. H. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00758-9 · Cited by 11 · see citing works
Mechanistic insights into differential requirement of receptor dimerization for oncogenic activation of mutant EGFR and its clinical perspective
Cho, J. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.3.025 · Cited by 11 · see citing works
Self-citation
Different EGF ‐induced receptor dimer conformations for signaling and internalization
Haubrich, J., Zwier, J. M., Charrier‐Savournin, F., Prézeau, L., & Pin, J. (2023) · The FASEB Journal · doi:10.1096/fj.202301209r · Cited by 10 · see citing works
Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)
Hayashi, H., Yonesaka, K., Nakamura, A., Fujimoto, D., Azuma, K., Sakata, S., TACHIHARA, M. Y., Ikeda, S., Yokoyama, T., Hataji, O., et al. (2022) · Lung Cancer · doi:10.1016/j.lungcan.2022.04.004 · Cited by 10 · see citing works
Self-citation
EGFR degraders in non‐small‐cell lung cancer: Breakthrough and unresolved issue
Shen, J., Chen, L., Liu, J., Li, A., Zheng, L., Chen, S., & Li, Y. (2024) · Chemical Biology & Drug Design · doi:10.1111/cbdd.14517 · Cited by 9 · see citing works
Self-citation
Autophosphorylation of the carboxyl‐terminal domain is not required for oncogenic transformation by lung‐cancer derived EGFR mutants
Cho, J., Kim, S., Du, J., & Meyerson, M. M. (2018) · International Journal of Cancer · doi:10.1002/ijc.31332 · Cited by 9 · see citing works
Self-citation
First-line Osimertinib in EGFR Mutation-Positive Non-Small Cell Lung Cancer Patients with Poor Performance Status
Takamizawa, S., Okuma, Y., Kato, Y. X., Hakozaki, T., Kitagawa, S., & Zenke, Y. (2021) · Future Oncology · doi:10.2217/fon-2021-0947 · Cited by 8 · see citing works
Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer
Kaneda, T., Yoshioka, H., Tamiya, M., Tamiya, A., Hata, A., Okada, A., Niwa, T., Shiroyama, T., Kanazu, M., Ishida, T., et al. (2018) · BMC Cancer · doi:10.1186/s12885-017-3952-7 · Cited by 9 · see citing works
Absence of copy number gain ofEGFR: A possible predictive marker of long‐term response to afatinib
Nakamura, T., Sato, A., Nakashima, C., Abe, T., Iwanaga, K., Umeguchi, H., Kawaguchi, A., & Sueoka‐Aragane, N. (2022) · Cancer Science · doi:10.1111/cas.15655 · Cited by 8 · see citing works
From targeted therapy to a novel way: Immunogenic cell death in lung cancer
Xu, J., Xiong, Y., Xu, Z., Xing, H., Zhou, L., & Zhang, X. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.1102550 · Cited by 8 · see citing works
Furmonertinib in uncommon EGFR ‐mutated non‐small cell lung cancer with central nervous system metastases: A retrospective cohort study
Xie, Y., Fang, H., Cheng, W., Xu, T., Xu, S. Q., Yu, C., Liu, Y., & Fang, S. (2025) · International Journal of Cancer · doi:10.1002/ijc.35460 · Cited by 7 · see citing works
The role of kinase domain dimerization in EGFR activation
Petrova, Z. O., Han, L., Tsutsui, Y., Sheetz, J. B., Ashtekar, K. D., & Lemmon, M. A. (2025) · Structure · doi:10.1016/j.str.2025.11.017 · Cited by 7 · see citing works
Highly Specific Cytokine Receptor‐Targeting Chimeras for Targeted Membrane Protein Degradation and Sensitization of Osimertinib in EGFR‐Mutated Non‐Small‐Cell Lung Cancer
Wu, J., Gao, Q., Xia, Q., Wang, Y., Zheng, Z., He, A., Liu, Y., Yang, Y., Miao, Y., & Han, D. (2025) · Advanced Materials · doi:10.1002/adma.202504050 · Cited by 7 · see citing works
Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor
Hu, Z., Hu, Y., Liu, X., Xi, R., Zhang, A., Liu, D., Xie, Q., & Chen, L. (2015) · Oncotarget · doi:10.18632/oncotarget.5221 · Cited by 6 · see citing works
Self-citation
Mutant forms of EGFR promote HER2 trafficking through efficient formation of HER2-EGFR heterodimers
Tsutsumi, H., Iwama, E., Ibusuki, R., Shimauchi, A., Ota, K., Yoneshima, Y., Inoue, H., Tanaka, K., Nakanishi, Y., & Okamoto, I. (2022) · Lung Cancer · doi:10.1016/j.lungcan.2022.11.018 · Cited by 8 · see citing works
Structural Perspectives in the Development of Novel EGFR Inhibitors for the Treatment of NSCLC
Makhija, R., Sharma, A., Dubey, R., & Asati, V. (2024) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575296174240323172754 · Cited by 5 · see citing works
Osimertinib as First-Line Treatment for Patients With Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in a Real-World Setting: Updated Overall Survival Data (OSI-FACT-OS)
Sakata, Y., Saito, G., Sakata, S., Yamaguchi, T., Tamiya, M., Suzuki, H., Shibaki, R., Okada, A., Yokoyama, T., Matsumoto, H., et al. (2025) · Clinical Lung Cancer · doi:10.1016/j.cllc.2025.05.015 · Cited by 5 · see citing works
Monomer Preference of EGFR Tyrosine Kinase Inhibitors Influences the Synergistic Efficacy of Combination Therapy with Cetuximab
Oashi, A., Yasuda, H., Kobayashi, K., Tani, T., Hamamoto, J., Masuzawa, K., Manabe, T., Terai, H., Ikemura, S., Kawada, I., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1036 · Cited by 4 · see citing works
Classification and regression tree for estimating predictive markers to detect T790M mutations after acquired resistance to first line EGFR-TKI: HOPE-002
Tamiya, M., Fujikawa, K., Suzuki, H., Yokoyama, T., Uenami, T., Tamiya, A., Sato, Y., Saito, G., Uchida, J., Morita, M., et al. (2022) · Investigational New Drugs · doi:10.1007/s10637-021-01203-5 · Cited by 5 · see citing works
Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the MousePreprint
Vaishnavi, A., Kinsey, C. G., & McMahon, M. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041385 · Cited by 5 · see citing works
Diverse perspectives on proteomic posttranslational modifications to address EGFR-TKI resistance in non-small cell lung cancer
Ma, Y., Zhang, F., Li, J., Li, J., & Li, Y. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1436033 · Cited by 5 · see citing works
Differences in growth promotion, drug response and intracellular protein trafficking of FLT3 mutants.
Mashkani, B., Griffith, R., & Ashman, L. K. (2014) · Europe PMC (PubMed Central) · Cited by 4 · see citing works
Functional loss of ERBB receptor feedback inhibitor 1 ( MIG6 ) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor ( EGFR )
Yi, S. A., Cho, D., Kim, S.-J., Kim, H., Choi, M. K., Choi, H. S., Shin, S., Yun, S., Lim, A., Jeong, J. K., et al. (2024) · Molecular Oncology · doi:10.1002/1878-0261.13717 · Cited by 3 · see citing works
Self-citation
Steric disruption of EGFR oligomerization overcomes therapy resistance in non–small cell lung cancer
Song, D., Jang, J., Lin, M. Z., & Jung, Y. (2025) · Science Advances · doi:10.1126/sciadv.ady7032 · Cited by 3 · see citing works
PINK1-Mediated Inhibition of EGFR Dimerization and Activation Impedes EGFR-Driven Lung Tumorigenesis
Lin, E. P.-Y., Huang, B., Lai, W., Tseng, Y., Yang, S., Kuo, H.-C., & Yang, P. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-2582 · Cited by 3 · see citing works
Intrinsic/proximal cell surface marker logic-gated extracellular targeted protein degradation in specific cell population
Wang, Y., Zhang, G., Rong, P., Guo, P., Huang, S., Yang, H., Wang, P., Tang, L., Li, X., Tang, X., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.05.002 · Cited by 3 · see citing works
EGFR-TKIs Combined with Allogeneic CD8+ NKT Cell Immunotherapy to Treat Patients with Advanced EGFR-Mutated Lung Cancer
Ye, F., Yuan, X., Yu, W., Ma, Y., Mao, C., Li, X., Li, J., Dai, C., Qian, F.-H., Li, J., et al. (2024) · Technology in Cancer Research & Treatment · doi:10.1177/15330338241273198 · Cited by 3 · see citing works
Early emergence of de novo EGFR T790M gatekeeper mutations during erlotinib treatment in PC9 non-small cell lung cancer cells
Kim, S.-J., Park, A. K., & Cho, J. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.06.065 · Cited by 3 · see citing works
Self-citation
Immunogenicity of Del19 EGFR mutations in Chinese patients affected by lung adenocarcinoma
Pan, D., Zhou, D., Cai, W., Wu, W., Tan, W. L., Zhou, C., & Lou, Y. (2019) · BMC Immunology · doi:10.1186/s12865-019-0320-1 · Cited by 3 · see citing works
Structural basis for EGFR transmembrane signaling and its implications in therapeutic development
Mi, L.-Z., ShaoWei, G. U., & XingXing, W. A. N. G. (2018) · Scientia Sinica Vitae · doi:10.1360/n052018-00007 · Cited by 2 · see citing works
Different conformations of EGF-induced receptor dimers involved in signaling and internalizationPreprint
Haubrich, J., Zwier, J. M., Charrier‐Savournin, F., Prézeau, L., & Pin, J. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.19.488777 · Cited by 3 · see citing works
Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Robles-Oteíza, C., Ayeni, D. O., Levy, S., Homer, R., Kaech, S. M., & Politi, K. A. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.049072 · Cited by 2 · see citing works
P-Glycoprotein (MDR1/ABCB1) Restricts Brain Accumulation of the Novel EGFR Inhibitor EAI045 and Oral Elacridar Coadministration Enhances Its Brain Accumulation and Oral Exposure
Wang, J., Susam, M. M., Gan, C., Sparidans, R. W., Lebre, M. C., Beijnen, J. H., & Schinkel, A. H. (2022) · Pharmaceuticals · doi:10.3390/ph15091124 · Cited by 2 · see citing works
Which is better, EGFR-TKI mono or combination for non-small cell lung cancer with mutated EGFR?
Tanzawa, S., Ishihara, M., Haruyama, T., Ochiai, R., Sakamoto, T., Honda, T., Ota, S., Ichikawa, Y., Watanabe, K., & Seki, N. (2019) · Translational Cancer Research · doi:10.21037/tcr.2019.08.18 · Cited by 2 · see citing works
A rotamer relay information system in the epidermal growth factor receptor–drug complexes reveals clues to new paradigm in protein conformational change
Hameduh, T., Mokry, M., Miller, A. D., Adam, V., Heger, Z., & Haddad, Y. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.09.026 · Cited by 2 · see citing works
Investigating osimertinib plus chemotherapy in EGFR-mutated advanced non-small cell lung cancer
Spagnuolo, A., & Gridelli, C. (2025) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2025.2464903 · Cited by 1 · see citing works
Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods
Burns, E. A., Matyas, B., Lidke, D. S., & Smith, A. W. (2025) · Biophysical Journal · doi:10.1016/j.bpj.2025.09.018 · Cited by 1 · see citing works

Abstract A177: Cetuximab resistance associated with dimerization-independence of oncogenic EGFR mutants
Cho, J., Chen, L., Sangji, N. F., Du, J., Okabe, T., Yonesaka, K., Francis, J. M., Flavin, R., Yu, S., Greulich, H. E., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-09-a177 · Cited by 1 · see citing works
Self-citation
Mechanistic insights into the activation of oncogenic forms of EGF receptor
Wang, Z., Longo, P. A., Tarrant, M. K., Kim, K., Head, S. A., Leahy, D. J., & Cole, P. A. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2168 · Cited by 94 · see citing works
Mechanistic insights into the activation of oncogenic forms of EGF receptor. Nat Struct Mol Biol 18: 1388–1393
Wang, Z., Longo, P. A., Tarrant, M. K., Kim, K., Head, S., Leahy, D. J., & Cole, P. A. (2011)
EGFR lung cancer mutants get specialized
Littlefield, P., & Jura, N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314719110 · Cited by 12 · see citing works
Enhanced dimerization drives ligand-independent activity of mutant epidermal growth factor receptor in lung cancer
Valley, C. C., Arndt‐Jovin, D. J., Karedla, N., Steinkamp, M. P., Chizhik, A. I., Hlavacek, W. S., Wilson, B. S., Lidke, K. A., & Lidke, D. S. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-05-0269 · Cited by 93 · see citing works

Authors: Cho, J., Chen, L., Sangji, N., Okabe, T., Yonesaka, K., Francis, J. M., Flavin, R. J., Johnson, W., Kwon, J., Yu, S., Greulich, H., Johnson, B. E., Eck, M. J., Jänne, P. A., Wong, K.-K., & Meyerson, M.
Affiliations: Broad Institute (US)
Authors' Affiliations: Departments of 1Medical Oncology and 2Cancer Biology; 3Center for Cancer Genome Discovery, 4Lowe Center for Thoracic Oncology, and 5Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute; Departments of 6Medicine, Brigham and Women's Hospital; Departments of 7Biological Chemistry and Molecular Pharmacology and 8Pathology, Harvard Medical School, Boston, Massachusetts; 9Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea; and 10The Broad Institute of Harvard and MIT, Cambridge, Massachusetts
Corresponding author: Cho, Jeonghee
Meyerson, Matthew
ORCID: Cho, Jeonghee
Chen, Liang
Sangji, Naveen
Yonesaka, Kimio
Francis, Joshua M.
Flavin, Richard J.
Greulich, Heidi
Johnson, Bruce E.
Eck, Michael J.
Wong, Kwok-Kin
Meyerson, Matthew
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2013-11-14
Volume: 73
Issue: 22
Pages: 6770-6779
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-13-1145
PMC: PMC3903789
OpenAlex: W1986412478
Cited by: 117
References: 55
Citations by year: 2026: 5 · 2025: 14 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 11 · 2020: 6 · 2019: 8 · 2018: 12 · 2017: 6 · 2016: 7 · 2015: 10 · 2014: 2 · 2013: 1
FWCI: 5.43
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Food and Drug Administration
National Cancer Institute (R01CA116020, P01CA154303)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: cetuximab, EGFR mutation, lung adenocarcinoma, L858R mutation, exon 19 deletion, exon 20 insertion, T790M mutation, kinase domain, receptor activation, oncogenic transformation, monoclonal antibody therapy, anticancer mechanism
MeSH terms: Cetuximab, Adenocarcinoma, Animals, Antineoplastic Agents, Cell Transformation, Neoplastic, Cells, Cultured, Humans, Lung Neoplasms, Protein Conformation, Amino Acid Substitution, NIH 3T3 Cells, Mice, Protein Multimerization, Antibodies, Monoclonal, Humanized, ErbB Receptors

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Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization

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