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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 2019 (8)

Title and authors Publication Year
Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis
BW Yoon, JH Kim, SH Lee, CM Choi, JK Rho, S Yoon, DH Lee, SW Kim, TW Jang, JC Lee
Translational oncology 2019
Role of cytokines in combinatorial immunotherapeutics of non‐small cell lung cancer through systems perspective
P Misra, S Singh
Cancer Medicine 2019
Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment
T Zhang, B Wan, Y Zhao, C Li, H Liu, T Lv, P Zhan, Y Song
Translational Lung Cancer Research 2019
On-target Resistance to the Mutant-Selective EGFR Inhibitor Osimertinib Can Develop in an Allele-Specific Manner Dependent on the Original EGFR-Activating Mutation
BP Brown, YK Zhang, D Westover, Y Yan, H Qiao, V Huang, Z Du, JA Smith, JS Ross, VA Miller, S Ali, L Bazhenova, AB Schrock, J Meiler, CM Lovly
Clinical cancer research 2019
Rethink of EGFR in Cancer With Its Kinase Independent Function on Board
R Thomas, Z Weihua
Frontiers in Oncology 2019
Targeting Autophagy for Overcoming Resistance to Anti-EGFR Treatments
Y Kwon, M Kim, HS Jung, Y Kim, D Jeoung
Cancers 2019
Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD‐L1)‐mediated immunosuppression
Q Xu, Q Long, D Zhu, D Fu, B Zhang, L Han, M Qian, J Guo, J Xu, L Cao, YE Chin, JP Coppé, EW Lam, J Campisi, Y Sun
Aging Cell 2019
Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models
PS Yee, NS Zainal, CP Gan, BK Lee, KS Mun, MT Abraham, SM Ismail, ZA Rahman, V Patel, SC Cheong
Targeted Oncology 2019

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