Novel mutant-selective EGFR kinase inhibitors against EGFR T790M
Open accessAbstract
The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clinically more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacological screens against clinically important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In 2009, Pasi et al. identified covalent pyrimidine EGFR inhibitors (WZ 3146, WZ 4002, WZ 8040) through screening a library of irreversible kinase inhibitors specific to EGFRT790M.
“In 2009, Pasi et al. identified a series of covalent pyrimidine EGFR inhibitors, including WZ 3146, WZ 4002, and WZ 8040, through screening a library of irreversible kinase inhibitors specific to EGFRT790M.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [203]
Third-generation EGFR-TKIs are designed to specifically inhibit mutant EGFR (19del-EGFR, L858R-EGFR and/or T790M+EGFR), sparing the WT receptor.
“These agents are designed to specifically inhibit mutant EGFR (ie, 19del-EGFR, L858R-EGFR and/or T790M+EGFR), sparing the WT receptor.14–18”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [14]
The T790M mutation was observed in approximately 50% of cases in which biopsy was obtained at relapse following gefitinib or erlotinib treatment in patients with exon 19 deletion or L858R EGFR mutation.
“The presence of the T790M mutation was observed in approximately 50% of the cases in which biopsy was obtained at the time of relapse following gefitinib or erlotinib treatment in patients with the exon 19 deletion or the L858R EGFR mutation.”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [14]
AZD9291 has a chemical structure distinct from WZ4002 and CO-1686.
“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 [34]
C797 lies opposite T790 in the ATP-binding pocket, forms a covalent bond with all third-generation EGFR TKIs, and is required for these inhibitors to suppress EGFR.
“C797 is located opposite T790 in the ATP binding pocket and forms a covalent bond with all third-generation TKIs and is necessary for the inhibitor to suppress EGFR (21).”
ENU mutagenesis has previously identified clinically relevant drug resistance mutations to EGFR TKIs.
“This approach has previously led to identification of clinically relevant drug resistance mutations to EGFR TKIs (30, 31).”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [30]
The T790M structural alteration enabled discovery of inhibitors that selectively inhibit T790M-bearing mutants, when in association with L858R or exon 19 deletions, relative to WT EGFR.
“Thus, the T790M structural alteration in essence “enabled” discovery of inhibitors that selectively inhibit T790M–bearing mutants, when in association with L858R or exon 19 deletions, relative to WT EGFR 58,59.”
From Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013) · cites this paper as [58]
The crystal structure of WZ4002 bound to EGFR T790M shows that L718 and L844 directly contact the inhibitor, with L718 contacting the aniline ring and L844 contacting the pyrimidine ring.
“Examination of the crystal structure of WZ4002 in complex with EGFR T790M (14) reveals that both L718 and L844 are in direct contact with the inhibitor; L718 primarily with the aniline ring and L844 with the pyrimidine ring (Figure 2A).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [14]
Cysteine 797 is the site of covalent binding for WZ4002, CO-1686, and AZD9291.
“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 [14]
The irreversible pyrimidine EGFR inhibitors WZ4002, CO-1686, and AZD9291 are more potent against T790M and selectively inhibit mutant over wild-type EGFR, which should improve efficacy and reduce toxicity compared with afatinib.
“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 [14]
C797 is the covalent binding site of WZ4002, and mutation to serine was previously shown to cause resistance.
“C797 is the site of covalent binding of WZ4002 and previously demonstrated to lead to drug resistance if mutated to serine (14).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [14]
CO-1686 is structurally more closely related to WZ4002 than to AZD9291, and in all models tested CO-1686 is very similar in vitro to WZ4002.
“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 [14]
ENU mutagenesis studies have been predictive of clinical drug resistance mutations in several prior studies.
“However, ENU mutagenesis studies have been predictive of clinical drug resistance mutations in several prior studies (14, 24).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [14]
Introduction of C797S into EGFR L858R/T790M or EGFR Del 19/T790M backgrounds resulted in significant loss of cellular potency for WZ4002 in prior studies.
“In prior studies, introduction of C797S into the background of EGFR L858R/T790M or EGFR Del 19/T790M resulted in significant loss of cellular potency for WZ4002 (14).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [14]
The non-covalent analogue of WZ4002, WZ4003, was ineffective in in vitro models of EGFR T790M.
“Analogously, a non-covalent analogue of WZ4002, WZ4003, was ineffective in in vitro models of EGFR T790M (14).”
From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [14]
Mutant-selective EGFR kinase inhibitors including WZ4002, CO-1686, and AZD9291 have demonstrated encouraging efficacy in preclinical models and in EGFR mutant NSCLC patients with EGFR T790M-mediated drug resistance.
“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 [14]
WZ4002 is a covalent pyrimidine EGFR inhibitor specifically designed against EGFR T790M that is 30-100 fold more potent against EGFR T790M, and up to 100 fold less potent against wild type EGFR than quinazoline based EGFR inhibitors in vitro, and is effective in murine models of lung cancer driven by EGFR T790M.
“WZ4002 is a covalent pyrimidine EGFR inhibitor specifically designed against EGFR T790M that is 30–100 fold more potent against EGFR T790M, and up to 100 fold less potent against wild type EGFR than quinazoline based EGFR inhibitors in vitro and is effective in murine models of lung cancer driven by EGFR T790M [84].”
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 [84]
Both 2G and 3G EGFR-TKIs are irreversible small-molecule inhibitors that covalently bind to EGFR kinase by targeting cysteine-797 in the ATP binding pocket, and 3G EGFR-TKIs are considered more specific for EGFR sensitizing mutations than 2G EGFR-TKIs.
“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”
Third-generation EGFR inhibitors selectively target T790M over wild-type EGFR, including osimertinib.
“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 [43]
Third-generation mutant-selective EGFR-TKIs have activity against cells that harbor TKI-sensitive EGFR mutations, and this activity is maintained in the presence of the T790M resistance mutation.
“Standard of care is rapidly changing with the development of third-generation, mutant-selective EGFR-TKIs that have activity against cells that harbor TKI-sensitive EGFR mutations. Unlike conventional EGFR-TKIs, this activity is maintained in the presence of T790M resistance mutation.8,9”
From Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non–Small-Cell Lung Cancer (2016) · cites this paper as [9]
Next-generation EGFR TKIs designed to target T790M produce high and durable responses in advanced EGFR-mutant NSCLC that has progressed after first- or second-generation EGFR TKIs.
“Next-generation EGFR TKIs have since been developed specifically to target the T790M mutation, 17,18 and they have demonstrated high and durable responses in patients with advanced EGFRmutant NSCLC who have been previously treated and in whom firstor second-generation EGFR TKIs have failed.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
<i>MET</i> 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 · see citing works
<i>EGFR</i> 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 · see citing works
Self-citationPao, 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 · see citing works
Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0904554 · Cited by 2,373 · see citing works
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
Yun, C.-H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K.-K., Meyerson, M., & Eck, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709662105 · Cited by 2,118 · see citing works
Self-citationBIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models
Li, D., Ambrogio, L., Shimamura, T., Kubo, S., Takahashi, M., Chirieac, L. R., Padera, R. F., Shapiro, G. I., Baum, A., Himmelsbach, F., et al. (2008) · Oncogene · doi:10.1038/onc.2008.109 · Cited by 1,447 · see citing works
Self-citationDiscovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
Tsai, J., Lee, J. T., Wang, W., Zhang, J., Cho, H., Mamo, S., Bremer, R., Gillette, S., Kong, J., Haass, N. K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711741105 · Cited by 1,346 · see citing works
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 · see citing works
Self-citationEngelman, J. A., Zejnullahu, K., Gale, C.-M., Lifshits, E., Gonzales, A. J., Shimamura, T., Zhao, F., Vincent, P. W., Naumov, G. N., Bradner, J. E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1885 · Cited by 730 · see citing works
Self-citationJi, 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
Self-citationEngelman, J. A., Mukohara, T., Zejnullahu, K., Lifshits, E., Borras, A. M., Gale, C.-M., Naumov, G. N., Yeap, B. Y., Jarrell, E., Sun, J., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28656 · Cited by 457 · see citing works
Carey, K. D., Garton, A. J., Romero, M. S., Kahler, J., Thomson, S., Ross, S., Park, F., Haley, J. D., Gibson, N., & Sliwkowski, M. X. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0453 · Cited by 445 · see citing works
Bradeen, H. A., Eide, C. A., O'Hare, T., Johnson, K. J., Willis, S. G., Lee, F. Y., Druker, B. J., & Deininger, M. W. (2006) · Blood · doi:10.1182/blood-2006-02-004580 · Cited by 393 · see citing works
Li, D., Shimamura, T., Ji, H., Chen, L., Haringsma, H. J., McNamara, K. L., Liang, M., Perera, S. A., Zaghlul, S., Borgman, C. L., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.06.005 · Cited by 242 · see citing works
Self-citationDissection of the Inflammatory Bowel Disease Transcriptome Using Genome-Wide cDNA Microarrays
Costello, C. M., Mah, N., Häsler, R., Rosenstiel, P. C., Waetzig, G. H., Hahn, A., Lu, T. T., Gürbüz, Y. S., Nikolaus, S., Albrecht, M., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020199 · Cited by 231 · see citing works
Micronutrient Sprinkles to Control Childhood Anaemia
Zlotkin, S. H., Schauer, C. S., Christofides, A., Sharieff, W., Tondeur, M. C., & Hyder, S. M. Z. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020001 · Cited by 225 · see citing works
Godin-Heymann, N., Ulkus, L., Brannigan, B. W., McDermott, U., Lamb, J. A., Maheswaran, S., Settleman, J. E., & Haber, D. A. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-2387 · Cited by 206 · see citing works
Ogino, A., Kitao, H., Hirano, S., Uchida, A., Ishiai, M., Kozuki, T., Takigawa, N., Takata, M., Kiura, K., & Tanimoto, M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0681 · Cited by 193 · see citing works
Janne, P. A., von Pawel, J., Cohen, R. B., Crinò, L., Butts, C. A., Olson, S. S., Eiseman, I. A., Chiappori, A., Yeap, B. Y., Lenehan, P. F., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.1336 · Cited by 120 · see citing works
Yonesaka, K., Zejnullahu, K., Lindeman, N. I., Homes, A. J., Jackman, D. M., Zhao, F., Rogers, A. M., Johnson, B. E., & Janne, P. A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0957 · Cited by 120 · see citing works
Lietha, D., & Eck, M. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003800 · Cited by 108 · see citing works
Self-citationAllele-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-citationO’Hare, T., Eide, C. A., Tyner, J. W., Corbin, A. S., Wong, M. J., Buchanan, S. G., Holme, K. R., Jessen, K. A., Tang, C. M., Lewis, H. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800587105 · Cited by 80 · see citing works
Janne, P. A., Schellens, J. H. M., Engelman, J. A., Eckhardt, S. G., Millham, R., Denis, L. J., Britten, C. D., Wong, S. G., Boss, D. S., & Camidge, D. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.8027 · Cited by 67 · see citing works
Breault, G. A., Ellston, R. P. A., Green, S. A., James, S., Jewsbury, P. J., Midgley, C. J., Pauptit, R. A., Minshull, C. A., Tucker, J. A., & Pease, J. E. (2003) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(03)00203-8 · Cited by 63 · see citing works
Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors
Alam, M., Beevers, R. E., Ceska, T., Davenport, R. J., Dickson, K. M., Fortunato, M., Gowers, L., Haughan, A. F., James, L. A., Jones, M. W., et al. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.03.078 · Cited by 62 · see citing works
Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase
Hur, W., Velentza, A. V., Kim, S., Flatauer, L. J., Jiang, X., Valente, D., Mason, D. E., Suzuki, M., Larson, B., Zhang, J., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.062 · Cited by 41 · see citing works
Self-citationGontarewicz, A., Balabanov, S., Keller, G., Panse, J., Schafhausen, P., Bokemeyer, C., Fiedler, W., Moll, J. K., & Brümmendorf, T. H. (2008) · Leukemia Research · doi:10.1016/j.leukres.2008.04.012 · Cited by 19 · see citing works
Besse, B., Eaton, K. D., Soria, J., Lynch, T. J., Miller, V. A., Wong, K., Powell, C., Quinn, S., Zacharchuk, C., & Sequist, L. V. D. (2008) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(08)72135-9 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Genotypic 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 · see citing works
Cross, D. A. E., Ashton, S. E., Ghiorghiu, S., Eberlein, C., Nebhan, C. A., Spitzler, P. J., Orme, J. P., Finlay, M. R. V., Ward, R. A., Mellor, M. J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0337 · Cited by 2,246 · see citing works
Integrating liquid biopsies into the management of cancer
Siravegna, G., Marsoni, S., Siena, S., & Bardelli, A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.14 · Cited by 1,941 · see citing works
Liquid biopsy: monitoring cancer-genetics in the blood
Crowley, E. H., Nicolantonio, F. D., Loupakis, F., & Bardelli, A. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.110 · Cited by 1,821 · see citing works
Thress, K. S., Paweletz, C. P., Felip, E., Cho, B. C., Stetson, D., Dougherty, B., Lai, Z., Markovets, A., Vivancos, A., Kuang, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3854 · Cited by 1,589 · see citing works
Self-citationMechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers
Katayama, R., Shaw, A. T., Khan, T. M., Mino-Kenudson, M. A., Solomon, B., Halmos, B., Jessop, N. A., Wain, J. C., Yeo, A. T., Benes, C. H., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003316 · Cited by 1,316 · see citing works
Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery
Paulsen, C. E., & Carroll, K. S. (2013) · Chemical Reviews · doi:10.1021/cr300163e · Cited by 1,282 · see citing works
Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A. B., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0310 · Cited by 1,237 · see citing works
Self-citationGridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T. S. K., Petrella, F., Spaggiari, L., & Rosell, R. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.9 · Cited by 1,121 · see citing works
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
Pao, W., & Chmielecki, J. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2947 · Cited by 1,083 · see citing works
The quest to overcome resistance to EGFR-targeted therapies in cancer
Chong, C. R., & Janne, P. A. (2013) · Nature Medicine · doi:10.1038/nm.3388 · Cited by 1,055 · see citing works
ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048 · see citing works
Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling
Wagle, N., Emery, C., Berger, M. F., Davis, M. J., Sawyer, A. M., Pochanard, P., Kehoe, S. M., Johannessen, C. M., MacConaill, L. E., Hahn, W. C., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.2312 · Cited by 996 · see citing works
Hata, A. N., Niederst, M. J., Archibald, H. L., Gomez-Caraballo, M., Siddiqui, F. M., Mulvey, H. E., Maruvka, Y. E., Ji, F., Bhang, H.-E. C., Krishnamurthy Radhakrishna, V., et al. (2016) · Nature Medicine · doi:10.1038/nm.4040 · Cited by 985 · see citing works
EGFR Mutations and Lung Cancer
Santos, G. D. C., Shepherd, F. A., & Tsao, M. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130206 · Cited by 948 · see citing works
Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors
Jia, Y., Yun, C., Park, E., Ercan, D., Manuia, M., Juarez, J., Xu, C., Rhee, K., Chen, T., Zhang, H., et al. (2016) · Nature · doi:10.1038/nature17960 · Cited by 933 · see citing works
Self-citationAcquired resistance to TKIs in solid tumours: learning from lung cancer
Camidge, D. R., Pao, W., & Sequist, L. V. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.104 · Cited by 862 · see citing works
Oxnard, G. R., Thress, K. S., Alden, R. S., Lawrance, R., Paweletz, C. P., Cantarini, M., Yang, J. C.-H., Barrett, J. C., & Jänne, P. A. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.66.7162 · Cited by 850 · see citing works
Advances in covalent drug discovery
Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823 · see citing works
Wu, S., & Shih, J. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0777-1 · Cited by 788 · see citing works
Oxnard, G. R., Paweletz, C. P., Kuang, Y., Mach, S. L., O'Connell, A., Messineo, M. M., Luke, J. J., Butaney, M., Kirschmeier, P., Jackman, D. M., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2482 · Cited by 786 · see citing works
Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab
Yonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002442 · Cited by 663 · see citing works
Self-citationDeveloping Irreversible Inhibitors of the Protein Kinase Cysteinome
Liu, Q., Sabnis, Y. A., Zhao, Z., Zhang, T., Buhrlage, S. J., Jones, L. H., & Gray, N. S. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.12.006 · Cited by 662 · see citing works
Self-citationRB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer
Niederst, M. J., Sequist, L. V., Poirier, J. T., Mermel, C. H., Lockerman, E. L., Garcia, A. R., Katayama, R., Costa, C., Ross, K. N., Moran, T., et al. (2015) · Nature Communications · doi:10.1038/ncomms7377 · Cited by 647 · see citing works
CH5424802, a Selective ALK Inhibitor Capable of Blocking the Resistant Gatekeeper Mutant
Sakamoto, H., Tsukaguchi, T., Hiroshima, S., Kodama, T., Kobayashi, T., Fukami, T. A., Oikawa, N., Tsukuda, T., Ishii, N., & Aoki, Y. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.004 · Cited by 645 · see citing works
Finlay, M. R. V., Anderton, M., Ashton, S., Ballard, P., Bethel, P. A., Box, M. R., Bradbury, R. H., Brown, S. J., Butterworth, S., Campbell, A., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500973a · Cited by 636 · see citing works
Oxnard, G. R., Arcila, M. E., Sima, C. S., Riely, G. J., Chmielecki, J., Kris, M. G., Pao, W., Ladanyi, M., & Miller, V. A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2692 · Cited by 627 · see citing works
Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer
Harrison, P. T., Vyse, S., & Huang, P. H. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.09.015 · Cited by 625 · see citing works
Walter, A. O., Sjin, R. T. T., Haringsma, H. J., Ohashi, K., Sun, J., Lee, K., Dubrovskiy, A., Labenski, M., Zhu, Z., Wang, Z., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0314 · Cited by 620 · see citing works
Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer
Vaishnavi, A., Capelletti, M., Le, A. T., Kako, S. L., Butaney, M., Ercan, D., Mahale, S., Davies, K. D., Aisner, D. L., Pilling, A. B., et al. (2013) · Nature Medicine · doi:10.1038/nm.3352 · Cited by 615 · see citing works
Self-citationYasuda, H., Kobayashi, S., & Costa, D. B. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70129-2 · Cited by 610 · see citing works
Sabbah, D. A., Hajjo, R., & Sweidan, K. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200303123102 · Cited by 606 · see citing works
A Novel ALK Secondary Mutation and EGFR Signaling Cause Resistance to ALK Kinase Inhibitors
Sasaki, T., Koivunen, J. P., Ogino, A., Yanagita, M., Nikiforow, S., Zheng, W., Lathan, C. S., Marcoux, J. P., Du, J., Okuda, K., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1340 · Cited by 599 · see citing works
Self-citationNiederst, M. J., Hu, H., Mulvey, H. E., Lockerman, E. L., Garcia, A. R., Piotrowska, Z., Sequist, L. V., & Engelman, J. A. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0560 · Cited by 583 · see citing works
Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells
Ramirez, M., Rajaram, S., Steininger, R. J., Osipchuk, D., Roth, M. A., Morinishi, L. S., Evans, L., Ji, W., Hsu, C.-H., Thurley, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms10690 · Cited by 581 · see citing works
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
Self-citationKatayama, R., Khan, T. M., Benes, C. H., Lifshits, E., Ebi, H., Rivera, V. M., Shakespeare, W. C., Iafrate, A. J., Engelman, J. A., & Shaw, A. T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019559108 · Cited by 546 · see citing works
Circumventing cancer drug resistance in the era of personalized medicine
Garraway, L. A., & Jänne, P. A. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0012 · Cited by 503 · see citing works
Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles
Serafimova, I. M., Pufall, M. A., Krishnan, S., Duda, K., Cohen, M. S., Maglathlin, R. L., McFarland, J. M., Miller, R. M., Frödin, M., & Taunton, J. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.925 · Cited by 496 · see citing works
Mechanisms of resistance to EGFR-targeted drugs: lung cancer
Morgillo, F., Della Corte, C. M., Fasano, M., & Ciardiello, F. (2016) · ESMO Open · doi:10.1136/esmoopen-2016-000060 · Cited by 476 · see citing works
Kurppa, K. J., Liu, Y., To, C., Zhang, T., Fan, M., Vajdi, A., Knelson, E. H., Xie, Y., Lim, K., Cejas, P., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.006 · Cited by 475 · see citing works
Self-citationEpidermal Growth Factor Receptor Tyrosine Kinase Inhibitor–Resistant Disease
Ohashi, K., Maruvka, Y. E., Michor, F., & Pao, W. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.3912 · Cited by 467 · see citing works
Challenges and Opportunities in Cancer Drug Resistance
Ward, R. A., Fawell, S. E., Floc’h, N., Flemington, V., McKerrecher, D., & Smith, P. D. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00383 · Cited by 453 · see citing works
Piotrowska, Z., Isozaki, H., Lennerz, J. K., Gainor, J. F., Lennes, I. T., Zhu, V. W., Marcoux, N., Banwait, M. K., Digumarthy, S. R., Su, W., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1022 · Cited by 447 · see citing works
Uchibori, K., Inase, N., Araki, M., Kamada, M., Sato, S., Okuno, Y., Fujita, N., & Katayama, R. (2017) · Nature Communications · doi:10.1038/ncomms14768 · Cited by 424 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer
Tan, C., Gilligan, D., & Pacey, S. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00246-6 · Cited by 390 · see citing works
Ayati, A., Moghimi, S., Salarinejad, S., Safavi, M., Pouramiri, B., & Foroumadi, A. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.103811 · Cited by 385 · see citing works
Drug-Induced Death Signaling Strategy Rapidly Predicts Cancer Response to Chemotherapy
Montero, J., Sarosiek, K. A., DeAngelo, J. D., Maertens, O., Ryan, J., Ercan, D., Piao, H., Horowitz, N. S., Berkowitz, R. S., Matulonis, U., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.042 · Cited by 378 · see citing works
Self-citationCardarella, S., Ogino, A., Nishino, M., Butaney, M., Shen, J., Lydon, C., Yeap, B. Y., Sholl, L. M., Johnson, B. E., & Janne, P. A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0657 · Cited by 375 · see citing works
EGFR signaling pathway as therapeutic target in human cancers
Levantini, E., Maroni, G., Re, M. D., & Tenen, D. G. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.04.002 · Cited by 372 · see citing works
EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors
Ercan, D., Choi, H. G., Yun, C.-H., Capelletti, M., Xie, T., Eck, M. J., Gray, N. S., & Jänne, P. A. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2789 · Cited by 368 · see citing works
Self-citationOxnard, G. R., Arcila, M. E., Chmielecki, J., Ladanyi, M., Miller, V. A., & Pao, W. J. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2571 · Cited by 355 · see citing works
Ten things you should know about protein kinases: IUPHAR R eview 14
Fabbro, D., Cowan‐Jacob, S. W., & Möbitz, H. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13096 · Cited by 350 · see citing works
Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor
To, C., Jang, J., Chen, T., Park, E., Mushajiang, M., Clercq, D. J. H. D., Xu, M., Wang, S., Cameron, M. D., Heppner, D. E., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0903 · Cited by 351 · see citing works
Self-citationEmerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer
Gainor, J. F., & Shaw, A. T. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.2029 · Cited by 349 · see citing works
Discovery of Potent and Selective Covalent Inhibitors of JNK
Zhang, T., Iñesta-Vaquera, F., Niepel, M., Zhang, J., Ficarro, S. B., Machleidt, T., Xie, T., Marto, J. A., Kim, N., Sim, T., et al. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.11.010 · Cited by 348 · see citing works
Self-citationSasaki, T., Okuda, K., Zheng, W., Butrynski, J. E., Capelletti, M., Wang, L., Gray, N. S., Wilner, K. D., Christensen, J. G., Demetri, G. D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2956 · Cited by 333 · see citing works
Self-citationAdvances in covalent kinase inhibitors
Abdeldayem, A., Raouf, Y. S., Constantinescu, S. N., Moriggl, R., & Gunning, P. T. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00720b · Cited by 332 · see citing works
Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks
Barf, T., & Kaptein, A. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3003203 · Cited by 331 · see citing works
Rosell, R., Molina, M. A., Costa, C., Simonetti, S., Gimenez-Capitan, A., Bertran-Alamillo, J., Mayo, C., Moran, T., Mendez, P., Cardenal, F., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2158 · Cited by 304 · see citing works
Eberlein, C. A., Stetson, D., Markovets, A. A., Al-Kadhimi, K. J., Lai, Z., Fisher, P. R., Meador, C. B., Spitzler, P. J., Ichihara, E., Ross, S. J., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3167 · Cited by 304 · see citing works
KLIFS: A Knowledge-Based Structural Database To Navigate Kinase–Ligand Interaction Space
van Linden, O. P. J., Kooistra, A. J., Leurs, R., de Esch, I. J. P., & de Graaf, C. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400378w · Cited by 303 · see citing works
EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance
Wang, S., Song, Y., & Liu, D. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.11.008 · Cited by 302 · see citing works
Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor
Lim, S. M., Westover, K. D., Ficarro, S. B., Harrison, R. A., Choi, H. G., Pacold, M. E., Carrasco, M., Hunter, J., Kim, N. D., Xie, T., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307387 · Cited by 300 · see citing works
Self-citationFibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors
Dai, S., Zhou, Z. M., Chen, Z., Xu, G., & Chen, Y. (2019) · Cells · doi:10.3390/cells8060614 · Cited by 297 · see citing works
Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors.
Ercan, D., Xu, C., Yanagita, M., Monast, C. S., Pratilas, C. A., Montero, J., Butaney, M., Shimamura, T., Sholl, L., Ivanova, E. V., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0103 · Cited by 294 · see citing works
Self-citationWard, R. A., Anderton, M. J., Ashton, S., Bethel, P. A., Box, M., Butterworth, S., Colclough, N., Chorley, C. G., Chuaqui, C., Cross, D. A. E., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400822z · Cited by 279 · see citing works
Covalent Inhibition in Drug Discovery
Ghosh, A. K., Samanta, I., Mondal, A., & Liu, W. R. (2019) · ChemMedChem · doi:10.1002/cmdc.201900107 · Cited by 265 · see citing works
Glioblastoma Therapy: Past, Present and Future
Obrador, E., Moreno-Murciano, P., Oriol‐Caballo, M., López‐Blanch, R., Pineda, B., Gutiérrez-Arroyo, J., Loras, A., Bonet, L. G. G., Martínez‐Cadenas, C., Estrela, J. M., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052529 · Cited by 263 · see citing works
Nagano, T., TACHIHARA, M. Y., & Nishimura, Y. (2018) · Cells · doi:10.3390/cells7110212 · Cited by 252 · see citing works
Zubair, T., & Bandyopadhyay, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032651 · Cited by 248 · see citing works
Molecular Biology of Lung Cancer: Clinical Implications
Larsen, J. E., & Minna, J. D. (2011) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2011.08.003 · Cited by 247 · see citing works
Acquired Resistance ofEGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor
Yu, H. A., Tian, S. K., Drilon, A. E. D. C., Borsu, L. A., Riely, G. J., Arcila, M. E., & Ladanyi, M. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.1066 · Cited by 245 · see citing works
Janne, P. A., Wang, X., Socinski, M. A., Crawford, J., Stinchcombe, T. E., Gu, L., Capelletti, M., Edelman, M. J., Villalona-Calero, M. A., Kratzke, R. A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.1315 · Cited by 241 · see citing works
Self-citationDifferential Inhibitor Sensitivity of Anaplastic Lymphoma Kinase Variants Found in Neuroblastoma
Bresler, S. C., Wood, A., Haglund, E. A., Courtright, J., Belcastro, L. T., Plegaria, J. S., Cole, K. A., Toporovskaya, Y., Zhao, H., Carpenter, E. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002950 · Cited by 237 · see citing works
The Cysteinome of Protein Kinases as a Target in Drug Development
Chaikuad, A., Koch, P., Laufer, S., & Knapp, S. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201707875 · Cited by 237 · see citing works
Natural Products for Cancer-Targeted Therapy: Citrus Flavonoids as Potent Chemopreventive Agents
Meiyanto, E., Hermawan, A., & Anindyajati, A. (2012) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2012.13.2.427 · Cited by 233 · see citing works
Epidermal growth factor receptor mutations in lung adenocarcinoma
Siegelin, M. D., & Borczuk, A. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.147 · Cited by 233 · see citing works
The role of MDM2 amplification and overexpression in therapeutic resistance of malignant tumors
Hou, H., Sun, D., & Zhang, X. (2019) · Cancer Cell International · doi:10.1186/s12935-019-0937-4 · Cited by 232 · see citing works
Recondo, G., Bahcall, M., Spurr, L. F., Che, J., Ricciuti, B., Leonardi, G. C., Lo, Y., Li, Y. Y., Lamberti, G., Nguyen, T. T., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3608 · Cited by 226 · see citing works
Yano, S., Yamada, T., Takeuchi, S., Tachibana, K., Minami, Y., Yatabe, Y., Mitsudomi, T., Tanaka, H., Kimura, T., Kudoh, S., et al. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31823ab0dd · Cited by 222 · see citing works
Recent Clinical Advances in Lung Cancer Management
Johnson, D. H., Schiller, J. H., & Bunn, P. A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.1228 · Cited by 221 · see citing works
EGFR and NF-κB: partners in cancer
Shostak, K., & Chariot, A. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.04.001 · Cited by 218 · see citing works
Haber, D. A., Gray, N. S., & Baselga, J. M. (2011) · Cell · doi:10.1016/j.cell.2011.03.026 · Cited by 215 · see citing works
Self-citationCharacterization of Torin2, an ATP-Competitive Inhibitor of mTOR, ATM, and ATR
Liu, Q., Xu, C., Kirubakaran, S., Zhang, X., Hur, W., Liu, Y., Kwiatkowski, N. P., Wang, J., Westover, K. D., Gao, P., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-1702 · Cited by 212 · see citing works
Self-citationDrug resistance to targeted therapies: Déjà vu all over again
Groenendijk, F. H., & Bernards, R. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.05.004 · Cited by 211 · see citing works
Molecular biology of lung cancer: Clinical implications
Fong, K. M., & Minna, J. D. (2002) · Clinics in Chest Medicine · doi:10.1016/s0272-5231(03)00062-5 · Cited by 210 · see citing works
The Ascension of Targeted Covalent Inhibitors
Singh, J. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02134 · Cited by 210 · see citing works
Combined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR -Mutant Lung Cancer
Tricker, E. M., Xu, C., Uddin, S., Capelletti, M., Ercan, D., Ogino, A., Pratilas, C. A., Rosen, N. X., Gray, N. S., Wong, K., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0063 · Cited by 207 · see citing works
Self-citationMakinoshima, H., Takita, M., Matsumoto, S., Yagishita, A., Owada, S., Esumi, H., & Tsuchihara, K. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.575464 · Cited by 204 · see citing works
Insights into the Aberrant Activity of Mutant EGFR Kinase Domain and Drug Recognition
Gajiwala, K. S., Feng, J., Ferre, R. A., Ryan, K., Brodsky, O., Weinrich, S. L., Kath, J. C., & Stewart, A. (2012) · Structure · doi:10.1016/j.str.2012.11.014 · Cited by 204 · see citing works
Wang, S., Tsui, S. T., Liu, C., Song, Y., & Liu, D. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0290-1 · Cited by 204 · see citing works
Rethink of EGFR in Cancer With Its Kinase Independent Function on Board
Thomas, R., & Weihua, Z. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00800 · Cited by 204 · see citing works
Wu, Q., Qian, W., Sun, X., & Jiang, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01362-9 · Cited by 202 · see citing works
Tan, D. S. W., Yom, S. S., Tsao, M. S., Pass, H. I., Kelly, K., Peled, N., Yung, R. C., Wistuba, I. I., Yatabe, Y., Unger, M., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.05.008 · Cited by 201 · see citing works
Progress with covalent small-molecule kinase inhibitors
Zhao, Z., & Bourne, P. E. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.035 · Cited by 200 · see citing works
EGFR-TKI resistance in NSCLC patients: mechanisms and strategies.
Lin, Y., Wang, X., & Jin, H. (2014) · Europe PMC (PubMed Central) · Cited by 198 · see citing works
EGFR-mutated lung cancer: a paradigm of molecular oncology
Zhang, Z., Stiegler, A. L., Boggon, T. J., Kobayashi, S., & Halmos, B. (2010) · Oncotarget · doi:10.18632/oncotarget.186 · Cited by 197 · see citing works
Leproult, É., Barluenga, S., Moras, D., Wurtz, J., & Winssinger, N. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101396q · Cited by 196 · see citing works
- Authors
- Zhou, W., Ercan, D., Chen, L., Yun, C.-H., Li, D., Capelletti, M., Cortot, A. B., Chirieac, L., Iacob, R. E., Padera, R., Engen, J. R., Wong, K.-K., Eck, M. J., Gray, N. S., & Jänne, P. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Brigham and Women's Hospital (US)
- Northeastern University (US)
- Corresponding author
- Gray, Nathanael S.
- ORCID
- Venue
- Nature
- Published
- 2009-12
- Volume
- 462
- Issue
- 7276
- Pages
- 1070-1074
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2879581
- OpenAlex
- W2133963438
- Cited by
- 1,013
- References
- 30
- Citations by year
- 2026: 32 · 2025: 43 · 2024: 39 · 2023: 60 · 2022: 46 · 2021: 55 · 2020: 62 · 2019: 55 · 2018: 66 · 2017: 84 · 2016: 82 · 2015: 75 · 2014: 71 · 2013: 82 · 2012: 54
- FWCI
- 45.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (R01AG2400401)
- National Cancer Institute (R01CA116020, R01CA122794, R01CA130876, R01CA11446, P50CA090578, R01CA135257, R01CA080942)
- National Institute of General Medical Sciences (R01GM070590)
- 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
- EGFR kinase inhibitors, mutant-selective inhibitors, irreversible kinase inhibitors, non-small cell lung cancer, drug resistance, co-crystallization, gatekeeper mutation
- MeSH terms
- Animals, Antineoplastic Agents, Drug Evaluation, Preclinical, Lung, Models, Chemical, Models, Molecular, Mutation, Phosphorylation, Drug Resistance, Neoplasm, NIH 3T3 Cells, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Mice, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
