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Citations to this article

Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer
Lucia Regales, … , Katerina A. Politi, William Pao
Lucia Regales, … , Katerina A. Politi, William Pao
Published September 14, 2009
Citation Information: J Clin Invest. 2009;119(10):3000-3010. https://doi.org/10.1172/JCI38746.
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Research Article Oncology Article has an altmetric score of 6

Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer

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Abstract

EGFR is a major anticancer drug target in human epithelial tumors. One effective class of agents is the tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. These drugs induce dramatic responses in individuals with lung adenocarcinomas characterized by mutations in exons encoding the EGFR tyrosine kinase domain, but disease progression invariably occurs. A major reason for such acquired resistance is the outgrowth of tumor cells with additional TKI-resistant EGFR mutations. Here we used relevant transgenic mouse lung tumor models to evaluate strategies to overcome the most common EGFR TKI resistance mutation, T790M. We treated mice bearing tumors harboring EGFR mutations with a variety of anticancer agents, including a new irreversible EGFR TKI that is under development (BIBW-2992) and the EGFR-specific antibody cetuximab. Surprisingly, we found that only the combination of both agents together induced dramatic shrinkage of erlotinib-resistant tumors harboring the T790M mutation, because together they efficiently depleted both phosphorylated and total EGFR. We suggest that these studies have immediate therapeutic implications for lung cancer patients, as dual targeting with cetuximab and a second-generation EGFR TKI may be an effective strategy to overcome T790M-mediated drug resistance. Moreover, this approach could serve as an important model for targeting other receptor tyrosine kinases activated in human cancers.

Authors

Lucia Regales, Yixuan Gong, Ronglai Shen, Elisa de Stanchina, Igor Vivanco, Aviva Goel, Jason A. Koutcher, Maria Spassova, Ouathek Ouerfelli, Ingo K. Mellinghoff, Maureen F. Zakowski, Katerina A. Politi, William Pao

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 Total
Citations: 2 6 3 3 8 6 8 6 16 14 22 25 21 11 11 8 1 171
Citation information
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Citations to this article in year 2020 (6)

Title and authors Publication Year
Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations
JH Starrett, AA Guernet, ME Cuomo, KE Poels, IK van Alderwerelt van Rosenburgh, A Nagelberg, D Farnsworth, KS Price, H Khan, KD Ashtekar, M Gaefele, D Ayeni, TF Stewart, A Kuhlmann, SM Kaech, AM Unni, R Homer, WW Lockwood, F Michor, SB Goldberg, MA Lemmon, PD Smith, DA Cross, K Politi
Cancer research 2020
Genome‐scale CRISPR screening identifies cell cycle and protein ubiquitination processes as druggable targets for erlotinib‐resistant lung cancer
J Lee, A Choi, SY Cho, Y Jun, D Na, A Lee, G Jang, JY Kwon, J Kim, S Lee, C Lee
Molecular Oncology 2020
Next‐Generation Cancer‐Specific Hybrid Theranostic Nanomaterials: MAGE‐A3 NIR Persistent Luminescence Nanoparticles Conjugated to Afatinib for In Situ Suppression of Lung Adenocarcinoma Growth and Metastasis
MH Chan, WT Huang, J Wang, RS Liu, M Hsiao
Advanced Science 2020
Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial
V Subbiah, EI Dumbrava, Y Jiang, KZ Thein, A Naing, DS Hong, S Fu, SA Piha-Paul, AM Tsimberidou, F Janku, F Meric-Bernstam, R Kurzrock, G Falchook
Experimental Hematology and Oncology 2020
[Studies and Progress of EGFR exon 20 Insertion Mutation in Non-small Cell Lung Cancer]
Wensheng Zhou, Wei Zhang, Baohui Han
Zhongguo fei ai za zhi = Chinese journal of lung cancer 2020
Use of Ex Vivo Patient-Derived Tumor Organotypic Spheroids to Identify Combination Therapies for HER2 Mutant Non–Small Cell Lung Cancer
E Ivanova, M Kuraguchi, M Xu, AJ Portell, L Taus, I Diala, AS Lalani, J Choi, ES Chambers, S Li, S Liu, T Chen, TU Barbie, GR Oxnard, JJ Haworth, KK Wong, SE Dahlberg, AA Aref, DA Barbie, M Bahcall, CP Paweletz, PA Jänne
Clinical cancer research 2020

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Referenced in 3 patents
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