The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC
Open accessPublished version of a preprint
Abstract
Patients with non–small cell lung cancer (NSCLC) with activating EGF receptor (EGFR) mutations initially respond to first-generation reversible EGFR tyrosine kinase inhibitors. However, clinical efficacy is limited by acquired resistance, frequently driven by the EGFRT790M mutation. CO-1686 is a novel, irreversible, and orally delivered kinase inhibitor that specifically targets the mutant forms of EGFR, including T790M, while exhibiting minimal activity toward the wild-type (WT) receptor. Oral administration of CO-1686 as single agent induces tumor regression in EGFR-mutated NSCLC tumor xenograft and transgenic models. Minimal activity of CO-1686 against the WT EGFR receptor was observed. In NSCLC cells with acquired resistance to CO-1686 in vitro, there was no evidence of additional mutations or amplification of the EGFR gene, but resistant cells exhibited signs of epithelial–mesenchymal transition and demonstrated increased sensitivity to AKT inhibitors. These results suggest that CO-1686 may offer a novel therapeutic option for patients with mutant EGFR NSCLC. Significance: We report the preclinical development of a novel covalent inhibitor, CO-1686, that irreversibly and selectively inhibits mutant EGFR, in particular the T790M drug-resistance mutation, in NSCLC models. CO-1686 is the first drug of its class in clinical development for the treatment of T790M-positive NSCLC, potentially offering potent inhibition of mutant EGFR while avoiding the on-target toxicity observed with inhibition of the WT EGFR. Cancer Discov; 3(12); 1404–15. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 1317
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In the citing paper
“Both 2G and 3G EGFR‐TKI are irreversible small‐molecule inhibitors that covalently bind to EGFR kinase by targeting the cysteine‐797 residue, located in the ATP binding pocket, and 3G EGFR‐TKI are considered to be more specific for EGFR sensitizing mutations than 2G EGFR‐TKI.12, 13, 14”
From Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? (2016) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Rociletinib (CO-1686; Clovis Oncology) is a small-molecule, orally available, mutant-selective covalent inhibitor of commonly mutated forms of EGFR, including exon 19 deletions, L858R, and T790M, but not exon 20 insertions.”
From Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer (2015) · cites this paper as [7]
In the citing paper
“Rociletinib (XegafriTM, CO-1686) (65), developed by Clovis Oncology, is a specific mutant agent for the treatment of NSCLC, belonging to the third-generation EGFR TKIs.190,191”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [190]
In the citing paper
“Additionally, covalent inhibitors can exhibit high selectivity for proteins with non-conserved residues between variant forms or protein family members [41].”
From The design and development of covalent protein-protein interaction inhibitors for cancer treatment (2020) · cites this paper as [41]
In the citing paper
“AZD9291 has a distinct chemical structure from the other third-generation TKIs, WZ4002 (34) and CO-1686 (35).”
From AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer (2014) · cites this paper as [35]
In the citing paper
“Indeed, pre-clinical reports have suggested that “third generation” agents can induce switching to multiple signaling mechanisms that bypass EGFR dependency such as ERK and AKT pathways (35, 61, 62).”
From AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer (2014) · cites this paper as [35]
In the citing paper
“Preclinical studies have confirmed that rociletinib has minimal activity against wild-type EGFR.7”
From Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer (2015) · cites this paper as [7]
In the citing paper
“Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M.”
From Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer (2015) · cites this paper as [7]
In the citing paper
“In xenograft models with EGFR-activating mutations alone or combined with T790M resistance mutations, rociletinib resulted in durable tumor shrinkage, 7 which was most marked when plasma concentrations were maintained at more than 200 ng per milliliter across the dosing interval.”
From Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer (2015) · cites this paper as [7]
In the citing paper
“Indeed, it seems that EGFR monoclonal antibodies 60 and EGFR WT kinase sparing covalent T790M selective TKIs 61 are ineffective in typical EGFR exon 20 insertion mutants.”
From Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013) · cites this paper as [61]
In the citing paper
“Cysteine 797 is the site of covalent binding for all three of these agents (14–16).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [15]
In the citing paper
“They are not only more potent on EGFR T790M, but also selectively inhibit mutant over WT EGFR and hence should lead to increased clinical efficacy and less toxicity compared with afatinib (14–16).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [15]
In the citing paper
“These include the development of mutant selective EGFR kinase inhibitors, including WZ4002, CO-1686 and AZD9291, which to date have demonstrated encouraging efficacy in both preclinical models and in EGFR mutant NSCLC patients with EGFR T790M mediated drug resistance (14–18).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [15]
In the citing paper
“CO-1686 is structurally more closely related to WZ4002 than to AZD9291 and in all of the models tested CO-1686 is very similar in vitro to WZ4002 (14–16).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [15]
In the citing paper
“Additional pre-clinical studies have also identified activation of MAPK signaling and IGF1R signaling as well as epithelial to mesenchymal (EMT) transition as potential resistance mechanisms to WZ4002 and CO-1686 (15, 19, 20).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [15]
In the citing paper
“In vitro and in vivo studies demonstrated that Rociletinib irreversibly and selectively inhibits mutant EGFR, including T790M mutation, with minimal activity against wild type EGFR, suggesting that drug tolerability to this agent may be superior to first and second generation EGFR inhibitors”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [85]
In the citing paper
“Osimertinib and rociletinib are 3rd generation EGFR-TKIs, both of which are reported to be effective in lung cancer cells harboring EGFR T790M in preclinical models [30, 32].”
In the citing paper
“A third generation of EGFR inhibitors followed afatinib; these covalent inhibitors selectively target the T790M mutant over wild-type EGFR, and include WZ4002 (Dana–Farber Cancer Institute)43, osimertinib44,45 and rociletinib (Clovis Oncology; CO-1686)46 (Fig. 2c).”
From Advances in covalent drug discovery (2022) · cites this paper as [46]
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Citations
Cites
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261 · cited 1×
“Patients with the most common EGFR mutations (L858R mutation in exon 21 and delE746-A750 deletions in exon 19) typically have good responses to therapy with first-generation reversible EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib or gefitinib (3-5).”
Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., Palmero, R., Garcia-Gomez, R., Pallares, C., Sanchez, J. M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70393-x · Cited by 5,489
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-citationEGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
Pao, 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 2×
“second site EGFR point mutation that results in the substitution of threonine with methionine at amino acid position 790 (T790M;(7-10)).”
BackgroundSelf-citationGenotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
Epidermal growth factor receptor mutations in lung cancer
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2088 · Cited by 3,170
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466
Yu, H. A., Arcila, M. E., Rekhtman, N., Sima, C. S., Zakowski, M. F., Pao, W., Kris, M. G., Miller, V. A., Ladanyi, M., & Riely, G. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2246 · Cited by 2,454
Self-citation
Cited by
Sorted by citations
Items 201–300 of 686
Basu, D., Richters, A., & Rauh, D. (2015) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2015.04.038 · Cited by 50
Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines
Guo, S. J., Qian, W., Cai, J., Zhang, L., Wery, J., & Li, Q. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3245 · Cited by 50
Liao, B.-C., Lin, C., Lee, J., & Yang, J. C. (2016) · Journal of Biomedical Science · doi:10.1186/s12929-016-0305-9 · Cited by 52
Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers
Simon, N. C., & FitzGerald, D. (2016) · Toxins · doi:10.3390/toxins8050137 · Cited by 50
Liu, M., Xu, S., Wang, Y., Li, Y., Li, Y., Zhang, H., Liu, H., & Chen, J. (2016) · Oncotarget · doi:10.18632/oncotarget.13069 · Cited by 50
Lamie, P. F., El-Kalaawy, A. M., Latif, N. S. A., Rashed, L. A., & Philoppes, J. N. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113222 · Cited by 50
Zhang, X., Zhang, Y., Wang, Y., Gupta, P., Zeng, L., Xu, M., Wang, X., Yang, D., & Chen, Z. (2016) · Molecules · doi:10.3390/molecules21091236 · Cited by 49
Zhao, B., Xiao, Z., Qi, J., Luo, R., Zhou, L., Zhang, Y., Hu, X., Tang, Q., Zheng, P., Xu, S., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.11.069 · Cited by 49
Yang, Y., Cheng, T.-Y., Huang, S.-M., Su, C., Yang, P.-W., Lee, J.-M., Chen, C.-K., Hsiao, M., Hua, K.-T., & Kuo, M.-L. (2017) · Oncogene · doi:10.1038/onc.2017.18 · Cited by 49
Predictive biomarkers in precision medicine and drug development against lung cancer
Fang, B., Mehran, R. J., Heymach, J. V., & Swisher, S. G. (2015) · 癌症：英文版 · doi:10.1186/s40880-015-0028-4 · Cited by 49
Yu, L., Huang, M., Xu, T., Tong, L., Yan, X.-E., Zhang, Z., Xu, Y., Yun, C., Xie, H., Ding, K., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.12.006 · Cited by 48
Liao, B.-C., Lin, C., Lee, J., & Yang, J. C. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.05.009 · Cited by 48
Sakuma, Y. (2017) · Pathology International · doi:10.1111/pin.12553 · Cited by 48
Xu, J., Wang, J., & Zhang, S. (2017) · Oncotarget · doi:10.18632/oncotarget.21164 · Cited by 52
Kannan, S., Venkatachalam, G., Lim, H. H., Surana, U., & Verma, C. S. (2018) · Chemical Science · doi:10.1039/c8sc01262h · Cited by 48
Yang, K., Chen, Y., Zhou, J., Ma, L., Shan, Y., Cheng, X., Wang, Y., Zhang, Z., Ji, X., Chen, L., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14793 · Cited by 48
Heuckmann, J. M., & Thomas, R. K. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv184 · Cited by 48
Wu, H. Y., Wang, A., Zhang, W., Wang, B., Chen, C., Wang, W., Chen, H., Ye, Z., Zhao, Z., Wang, L., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5182 · Cited by 48
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Ko, B., Paucar, D., & Halmos, B. (2017) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s117944 · Cited by 47
Aboulwafa, O. M., Daabees, H. G., & Badawi, W. A. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.103798 · Cited by 50
Slobbe, P., Windhorst, A. D., van Walsum, M., Smit, E. F., Niessen, H. G., Solca, F., Stehle, G., van Dongen, G. A. M. S., & Poot, A. J. (2015) · EJNMMI Research · doi:10.1186/s13550-015-0088-0 · Cited by 46
Fan, X., Yao, X., Xu, S., Wong, V. K. W., He, J., Ding, J., Xue, W., Mujtaba, T., Michelangeli, F., Huang, M., et al. (2015) · Scientific Reports · doi:10.1038/srep16348 · Cited by 46
Kinases inhibitors in lung cancer: From benchside to bedside
Singh, P. K., Singh, H., & Silakari, O. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.07.002 · Cited by 47
Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation
Wang, A., Yan, X.-E., Wu, H. Y., Wang, W., Chen, H., Cheng, C., Zhao, Z., Zhao, P., Li, X., Wang, L., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11951 · Cited by 47
Kim, S.-H., Song, Y., & Seo, H. R. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1050-1 · Cited by 49
Liu, X., Xu-Liu, Pang, X., Yuan, X. Y., Yu, G.-X., Li, Y.-R., Guan, Y.-F., Zhang, Y., Song, J., Zhang, Q., et al. (2021) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2021.116358 · Cited by 46
Targeting EGFR in lung cancer: Lessons learned and future perspectives
Steuer, C. E., & Ramalingam, S. S. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.05.004 · Cited by 46
Pirazzoli, V., Ayeni, D. O., Meador, C. B., Sanganahalli, B. G., Hyder, F., de Stanchina, E., Goldberg, S. B., Pao, W. J., & Politi, K. A. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0620 · Cited by 46
Self-citationCovalent EGFR Inhibitors: Binding Mechanisms, Synthetic Approaches, and Clinical Profiles
Hossam, M., Lasheen, D. S., & Abouzid, K. A. M. (2016) · Archiv der Pharmazie · doi:10.1002/ardp.201600063 · Cited by 45
The neuropilin 2 isoform NRP2b uniquely supports TGFβ-mediated progression in lung cancer
Gemmill, R. M., Nasarre, P., Nair-Menon, J. U., Cappuzzo, F., Landi, L. M., D’Incecco, A., Uramoto, H., Yoshida, T., Haura, E. B., Armeson, K. E., et al. (2017) · Science Signaling · doi:10.1126/scisignal.aag0528 · Cited by 45
Structural pharmacological studies on EGFR T790M/C797S
Kong, L., Ma, R., Yao, M.-Y., Yan, X.-E., Zhu, S., Zhao, P., & Yun, C. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.04.138 · Cited by 45
Ninomiya, K., Ohashi, K., Makimoto, G., Tomida, S., Higo, H., Kayatani, H., Ninomiya, T., Kubo, T., Ichihara, E., Hotta, K., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-20326-z · Cited by 45
Self-citationZeng, B., Ge, C., Li, R., Zhang, Z., Fu, Q., Li, Z., Lin, Z., Liu, L., Xue, Y., Xu, Y., et al. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109562 · Cited by 45
Emerging Agents and New Mutations in EGFR-Mutant Lung Cancer
Ayeni, D. O., Politi, K. A., & Goldberg, S. B. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1211 · Cited by 44
Hidaka, N., Iwama, E., Kubo, N., Harada, T., Miyawaki, K., Tanaka, K., Okamoto, I., Baba, E., Akashi, K., Sasaki, H., et al. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.02.019 · Cited by 44
Auranofin Enhances Ibrutinib's Anticancer Activity in EGFR-Mutant Lung Adenocarcinoma
Hu, J., Zhang, H., Cao, M., Wang, L., Wu, S., & Fang, B. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-1173 · Cited by 46
Ahmad, I., Shaikh, M., Surana, S. J., Ghosh, A., & Patel, H. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1844801 · Cited by 44
Structural basis of mutant-selectivity and drug-resistance related to CO-1686
Yan, X.-E., Zhu, S.-J., Liang, L., Zhao, P., Choi, H. G., & Yun, C.-H. (2017) · Oncotarget · doi:10.18632/oncotarget.18588 · Cited by 43
Managing Resistance to EFGR- and ALK-Targeted Therapies
Lovly, C. M., Iyengar, P., & Gainor, J. F. (2017) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_176251 · Cited by 43
Spira, A. E., Halmos, B., & Powell, C. A. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201504-0756up · Cited by 44
Wang, S., Zhang, R., Zhang, H., Wang, Y., Yang, D., Zhao, Y., Yan, G., Xu, G., Guan, H.-Y., Zhou, Y.-H., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113573 · Cited by 43
Zhao, Z., Xie, L., Xie, L., & Bourne, P. E. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b02041 · Cited by 43
Liu, C., Shaurova, T., Shoemaker, S. F., Petkovich, M. P., Hershberger, P. A., & Wu, Y. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00307 · Cited by 42
AXL receptor tyrosine kinase as a therapeutic target in NSCLC
Bivona, T. G., & Okimoto, R. A. (2015) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s60438 · Cited by 41
Sacher, A. G., Janne, P. A., & Oxnard, G. R. (2014) · Cancer · doi:10.1002/cncr.28723 · Cited by 42
Patel, H., Shaikh, M., Ahmad, I., Lokwani, D. K., & Surana, S. J. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1754918 · Cited by 41
Dyrstad, S. E., Lotsberg, M. L., Tan, T. Z., Pettersen, I. K. N., Hjellbrekke, S., Tusubira, D., Engelsen, A. S. T., Daubon, T., Mourier, A., Thiery, J. P., et al. (2021) · Cancers · doi:10.3390/cancers13050941 · Cited by 44
Coco, S., Truini, A., Alama, A., Bello, M. G. D., Venè, R., Garuti, A., Carminati, E., Rijavec, E., Genova, C., Barletta, G., et al. (2014) · Targeted Oncology · doi:10.1007/s11523-014-0344-7 · Cited by 40
Li, W., Li, Y., Zhang, H., Liu, M., Gong, H., Yuan, Y., Shi, R., Zhang, Z., Liu, C., Chen, C., et al. (2021) · Journal of Cancer · doi:10.7150/jca.56093 · Cited by 40
Overcoming Resistance to Targeted Therapies in Cancer
Redmond, K. L., Papafili, A., Lawler, M., & Schaeybroeck, S. V. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.09.028 · Cited by 39
Gou, L.-Y., Li, A., Yang, J., Zhang, X., Su, J., Yan, H., Xie, Z., Lou, N.-N., Liu, S. M., Dong, Z., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9697 · Cited by 39
lncRNA in the liver: Prospects for fundamental research and therapy by RNA interference
Smekalova, E. M., Kotelevtsev, Y. V., Leboeuf, D., Shcherbinina, E. Y., Fefilova, A. S., Zatsepin, T. S., & Koteliansky, V. (2016) · Biochimie · doi:10.1016/j.biochi.2016.06.007 · Cited by 41
Wang, L., Zhao, J., Yao, Y., Wang, C., Zhang, J., Shu, X. H., Sun, X., Li, Y., Liu, K., Yuan, H., et al. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.09.024 · Cited by 39
Hirano, T., Yasuda, H., Hamamoto, J., Nukaga, S., Masuzawa, K., Kawada, I., Naoki, K., Niimi, T., Mimasu, S., Sakagami, H., et al. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-1033 · Cited by 39
Hammoud, M. K., Yosef, H. K., Lechtonen, T., Aljakouch, K., Schuler, M., Alsaidi, W., Daho, I., Maghnouj, A., Hahn, S. A., El‐Mashtoly, S. F., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-33682-7 · Cited by 42
Ai, M., Wang, C., Tang, Z., Liu, K., Sun, X., Ma, T., Li, Y., Ma, X., Li, L., & Chen, L. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103408 · Cited by 39
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
Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors
Qin, X., Lv, Y., Liu, P., Li, Z., Hu, L., Zeng, C., & Yang, L. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.02.009 · Cited by 38
Chiba, M., Togashi, Y., Bannno, E., Kobayashi, Y., Nakamura, Y., Hayashi, H., Terashima, M., Velasco, M. A. D., Sakai, K., Fujita, Y., et al. (2017) · BMC Cancer · doi:10.1186/s12885-017-3263-z · Cited by 38
A drug discovery platform to identify compounds that inhibit EGFR triple mutants
Saraon, P., Snider, J. D., Kalaidzidis, Y. L., Wybenga-Groot, L. E., Weiss, K., Rai, A., Radulovich, N., Drecun, L., Vučković, N., Vučetić, A., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0484-2 · Cited by 38
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Sato, M., Fuchida, H., Shindo, N., Kuwata, K., Tokunaga, K., Xiao-Lin, G., Inamori, R., Hosokawa, K., Watari, K., Shibata, T., et al. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00574 · Cited by 38
Todsaporn, D., Mahalapbutr, P., Poo-arporn, R. P., Choowongkomon, K., & Rungrotmongkol, T. (2022) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2022.105787 · Cited by 38
Toward precision medicine with next-generation EGFR inhibitors in non-small-cell lung cancer
Popat, S., & Yap, T. A. (2014) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s55339 · Cited by 37
Proto, C., Imbimbo, M., Gallucci, R., Brissa, A., Signorelli, D., Vitali, M., Macerelli, M., Corrao, G., Ganzinelli, M., Greco, F. G., et al. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.10.16 · Cited by 37
Hao, Y., Lyu, J., Qu, R., Tong, Y., Sun, D., Fěng, F., Tong, L., Yang, T., Zhao, Z., Zhu, L., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00346 · Cited by 37
Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR
Bryan, M. C., Burdick, D. J., Chan, B. K., Chen, Y., Clausen, S., Dotson, J., Eigenbrot, C. W., Elliott, R. L., Hanan, E. J., Heald, R. A., et al. (2015) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00428 · Cited by 36
Li, H., Stokes, W., Chater, E., Roy, R., de Bruin, E. C., Hu, Y., Liu, Z., Smit, E. F., Heynen, G. J. J. E., Downward, J., et al. (2016) · Cell Discovery · doi:10.1038/celldisc.2016.31 · Cited by 36
Osimertinib (AZD9291) increases radio‑sensitivity in EGFR T790M non‑small cell lung cancer
Wang, N., Wang, L., Meng, X., Wang, J., Zhu, L., Liu, C., Li, S., Li, Z., Yang, Z., Xing, L., et al. (2018) · Oncology Reports · doi:10.3892/or.2018.6803 · Cited by 36
Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond
Karachaliou, N., Rosell, R., Morales-Espinosa, D., & Viteri, S. (2014) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.2014.896210 · Cited by 35
Liang, Z., Cheng, Y., Chen, Y., Hu, Y., Liu, W.-P., Lü, Y., Wang, J., Wang, Y., Wu, G., Ying, J., et al. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.06.008 · Cited by 36
Targeting MERTK and AXL in EGFR Mutant Non-Small Cell Lung Cancer
Yan, D., Earp, H. S., DeRyckere, D., & Graham, D. K. (2021) · Cancers · doi:10.3390/cancers13225639 · Cited by 35
Li, H., Tong, C. W. S., Leung, Y., Wong, M., To, K. K. W., & Leung, K. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00288 · Cited by 34
Das, D., Wang, J., & Hong, J. (2021) · ChemMedChem · doi:10.1002/cmdc.202100166 · Cited by 35
ErbB polymorphisms: insights and implications for response to targeted cancer therapeutics
Alaoui‐Jamali, M. A., Morand, G. B., & da Silva, S. D. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00017 · Cited by 34
Xu, T., Peng, T., Ren, X., Zhang, L., Yu, L., Luo, J., Zhang, Z., Tu, Z., Tong, L., Huang, Z., et al. (2015) · MedChemComm · doi:10.1039/c5md00208g · Cited by 34
Sun, D., Yu, Y., Lyu, J., Zhou, W., Song, W., Zhao, Z., Chen, Z., Xu, Y. F., & Li, H. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00374 · Cited by 34
Wang, A., Li, X., Wu, H., Zou, F., Yan, X.-E., Cheng, C., Hu, C., Yu, K., Wang, W., Zhao, P., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01907 · Cited by 35
FBXW 7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy
Xiao, Y., Yin, C., Wang, Y., Lv, H., Wang, W., Huang, Y., Pérez‐Losada, J., Snijders, A. M., Mao, J., & Zhang, P. (2018) · Molecular Oncology · doi:10.1002/1878-0261.12200 · Cited by 34
Going for broke: targeting the human cancer pseudokinome
Bailey, F. P., Byrne, D. P., McSkimming, D. I., Kannan, N., & Eyers, P. A. (2015) · Biochemical Journal · doi:10.1042/bj20141060 · Cited by 33
Xu, S., Xu, T., Zhang, L., Zhang, Z., Luo, J., Liu, Y., Lu, X., Tu, Z., Ren, X., & Ding, K. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4012388 · Cited by 33
Das, D., Xie, L., Wang, J., Shi, J., & Hong, J. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.103790 · Cited by 33
Yang, T., Zhang, W., Cao, S., Sun, S., Cai, X., Xu, L., Li, P., Zheng, Z., & Li, S. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113984 · Cited by 33
Pawara, R. H., Ahmad, I., Nayak, D., Belamkar, S., Surana, S. J., Kundu, C. N., Patil, C., & Patel, H. (2021) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2021.132313 · Cited by 33
Yu, H., Li, Y., Yang, G., Song, Z., Wang, C., Huang, S., Jin, Y., Han, X., Zhen, Y., Liu, K., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.01.045 · Cited by 33
Yan, D., Parker, R. E., Wang, X., Frye, S. V., Earp, H. S., DeRyckere, D., & Graham, D. K. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0040 · Cited by 33
Zhang, L., Yang, Y., Zhou, H.-J., Zheng, Q., Li, Y., Zheng, S., Zhao, S., Chen, D., & Fan, C. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.08.026 · Cited by 33
Characterization of Covalent-Reversible EGFR Inhibitors
Smith, S. P., Keul, M., Engel, J., Basu, D., Eppmann, S., & Rauh, D. (2017) · ACS Omega · doi:10.1021/acsomega.7b00157 · Cited by 33
Patel, H., Ansari, A., Pawara, R. H., Ansari, I., Jadhav, H., & Surana, S. J. (2018) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2018.1557207 · Cited by 32
Tai, F., Gong, K., Song, K., He, Y., & Shi, J. (2020) · Nature Communications · doi:10.1038/s41467-019-14083-4 · Cited by 32
Patel, H., Ahmad, I., Jadhav, H., Pawara, R. H., Lokwani, D. K., & Surana, S. J. (2020) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207323666201204125524 · Cited by 32
Xiao, Q., Qu, R., Gao, D., Qi, Y., Tong, L., Zhang, W., Ding, J., Xie, H., & Li, Y. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.04.032 · Cited by 32
Engel, J., Smith, S. P., Lategahn, J., Tumbrink, H. L., Goebel, L., Becker, C., Hennes, E., Keul, M., Unger, A., Müller, H., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00515 · Cited by 32
Yang, K., Li, J., Zhao, J., Ren, P., Wang, Z., Wei, B., Dong, B., Sun, R., Wang, X., Groen, H. J. M., et al. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b01776 · Cited by 32
Self-citationMizuuchi, H., Suda, K., Murakami, I., Sakai, K., Sato, K., Kobayashi, Y., Shimoji, M., Chiba, M., Sesumi, Y., Tomizawa, K., et al. (2016) · Cancer Science · doi:10.1111/cas.12905 · Cited by 31
Kelly, R. J., Shepherd, F. A., Krivoshik, A., Jie, F., & Horn, L. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz128 · Cited by 31
NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor
Galvani, E., Sun, J., León, L. G., Sciarrillo, R., Narayan, R. S., Sjin, R. T. T., Lee, K., Ohashi, K., Heideman, D. A. M., Alfieri, R. R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3956 · Cited by 32
Self-citationGreig, M. J., Niessen, S., Weinrich, S. L., Feng, J. L., Shi, M., & Johnson, T. O. (2015) · International Journal of Cell Biology · doi:10.1155/2015/798936 · Cited by 31
Song, Z., Jin, Y., Yang, G., Wang, C., Zhang, J., Tang, Z., Peng, J., Liu, K., Li, Y., & Ma, X. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.09.001 · Cited by 31
Jang, J., Son, J., Park, E., Kosaka, T., Saxon, J. A., Clercq, D. J. H. D., Choi, H. G., Tanizaki, J., Eck, M. J., Janne, P. A., et al. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201805187 · Cited by 32
Inhibiting Epidermal Growth Factor Receptor at a Distance
Sinclair, J. K.-L., Denton, E. V., & Schepartz, A. (2014) · Journal of the American Chemical Society · doi:10.1021/ja504076t · Cited by 30
Metadata
- Authors
- Walter, A. O., Sjin, R. T. T., Haringsma, H. J., Ohashi, K., Sun, J., Lee, K., Dubrovskiy, A., Labenski, M., Zhu, Z., Wang, Z., Sheets, M., St Martin, T., Karp, R., van Kalken, D., Chaturvedi, P., Niu, D., Nacht, M., Petter, R. C., Westlin, W., Lin, K., Jaw-Tsai, S., Raponi, M., Van Dyke, T., Etter, J., Weaver, Z., Pao, W., Singh, J., Simmons, A. D., Harding, T. C., & Allen, A.
- Affiliations
- Vanderbilt University (US)
- Authors' Affiliations: 1Clovis Oncology Inc., San Francisco, California; 2Celgene Avilomics Research, Bedford, Massachusetts; 3Division of Hematology-Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; 4Mouse Cancer Genetics Program; and 5Center for Advanced Preclinical Research, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, Maryland
- Corresponding author
- Harding, Thomas C.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2013-12-01
- Volume
- 3
- Issue
- 12
- Pages
- 1404-1415
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC4048995
- OpenAlex
- W2146418087
- Cited by
- 620
- References
- 43
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 21 · 2023: 29 · 2022: 32 · 2021: 41 · 2020: 51 · 2019: 44 · 2018: 61 · 2017: 87 · 2016: 92 · 2015: 86 · 2014: 44 · 2013: 3
- FWCI
- 62.72
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- other-oa
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (P30 CA 68485, R01CA121210, P01CA129243, HHSN261200800001E), U54CA143798, P30CA068485)
- 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 › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- EGFR tyrosine kinase inhibitors, T790M mutation, acquired drug resistance, non-small cell lung cancer, irreversible kinase inhibitors, epithelial-mesenchymal transition, AKT inhibitors, on-target toxicity
- MeSH terms
- Acrylamides, Administration, Oral, Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Drug Screening Assays, Antitumor, Female, Humans, Lung Neoplasms, Mice, Inbred BALB C, Mice, Nude, Mice, Transgenic, Pyrimidines, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Mutant Proteins, Mice, HEK293 Cells, Epithelial-Mesenchymal Transition, Molecular Targeted Therapy, ErbB Receptors
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