HER2 Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR -Mutant Lung Cancers That Lack the Second-Site EGFR T790M Mutation
Open accessPublished version of a preprint
Abstract
Abstract EGF receptor (EGFR)–mutant lung cancers eventually become resistant to treatment with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models and human patients. Because afatinib is also a potent HER2 inhibitor, we investigated the role of HER2 in EGFR-mutant tumor cells. We show in vitro and in vivo that afatinib plus cetuximab significantly inhibits HER2 phosphorylation. HER2 overexpression or knockdown confers resistance or sensitivity, respectively, in all studied cell line models. FISH analysis revealed that HER2 was amplified in 12% of tumors with acquired resistance versus only 1% of untreated lung adenocarcinomas. Notably, HER2 amplification and EGFRT790M were mutually exclusive. Collectively, these results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EGFR-mutant tumors with acquired resistance to EGFR-TKIs. Significance: Because all EGFR-mutant lung adenocarcinomas eventually develop resistance to TKI therapy, understanding mechanisms of acquired resistance may improve clinical outcomes. These results implicate HER2 as a novel protein involved in the sensitivity or resistance of EGFR-mutant lung cancer and provide a rationale to assess the status of and possibly target HER2 in such tumors. Cancer Discov; 2(10); 922–33. ©2012 AACR. Read the Commentary on this article by Blakely and Bivona, p. 872. This article is highlighted in the In This Issue feature, p. 857.
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 a subset of EGFR mutant lung cancers, amplification of HER2, presumably involving HER3 reactivation, was identified as a resistance mechanism to EGFR TKIs.
“In a subset of EGFR mutant lung cancers, amplification of HER2, presumably involving HER3 reactivation, was also identified as a resistance mechanism to EGFR TKIs (Takezawa et al., 2012).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Takezawa et al., 2012
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
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486 · see citing works
<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368 · see citing works
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
Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Maemondo, M., Inoue, A., Kobayashi, K., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909530 · Cited by 5,525 · 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
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 · see citing works
Self-citationThe landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017 · see citing works
Self-citation<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
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 · see citing works
Self-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 · see citing works
Bean, J., Brennan, C., Shih, J.-Y., Riely, G., Viale, A., Wang, L., Chitale, D., Motoi, N., Szoke, J., Broderick, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710370104 · Cited by 1,598 · 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
Miller, V. A., Hirsh, V., Cadranel, J., Chen, Y.-M., Park, K., Kim, S.-W., Zhou, C., Su, W.-C., Wang, M., Sun, Y., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70087-6 · Cited by 961 · see citing works
Self-citationBertotti, A., Migliardi, G., Galimi, F., Sassi, F., Torti, D., Isella, C., Corà, D., Di Nicolantonio, F., Buscarino, M., Petti, C., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0109 · Cited by 939 · 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
Arcila, M. E., Oxnard, G. R., Nafa, K., Riely, G. J., Solomon, S. B., Zakowski, M. F., Kris, M. G., Pao, W., Miller, V. A., & Ladanyi, M. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2277 · Cited by 574 · see citing works
Self-citationOptimization of Dosing for EGFR-Mutant Non–Small Cell Lung Cancer with Evolutionary Cancer Modeling
Chmielecki, J., Foo, J., Oxnard, G. R., Hutchinson, K. E., Ohashi, K., Somwar, R., Wang, L., Amato, K. R., Arcila, M. E., Sos, M. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002356 · Cited by 519 · see citing works
Self-citationEngelman, J. A., Janne, P. A., Mermel, C. H., Pearlberg, J., Mukohara, T., Fleet, C., Cichowski, K. M., Johnson, B. E., & Cantley, L. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409773102 · Cited by 494 · see citing works
Wang, S. E., Narasanna, A., Pérez-Torres, M., Xiang, B., Wu, F. Y., Yang, S., Carpenter, G. F., Gazdar, A. F., Muthuswamy, S. K., & Arteaga, C. L. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.05.023 · Cited by 474 · see citing works
Regales, L., Gong, Y., Shen, R., de Stanchina, E., Vivanco, I., Goel, A. J., Koutcher, J. A., Spassova, M. K., Ouerfelli, O., Mellinghoff, I. K., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38746 · Cited by 371 · see citing works
Self-citationCappuzzo, F., Varella-Garcia, M., Shigematsu, H., Domenichini, I., Bartolini, S., Ceresoli, G. L., Rossi, E., Ludovini, V., Gregorc, V., Toschi, L., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.09.111 · Cited by 369 · see citing works
Oxnard, 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
Self-citationGong, Y., Somwar, R., Politi, K. A., Balak, M. N., Chmielecki, J., Jiang, X., & Pao, W. J. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040294 · Cited by 322 · see citing works
Self-citationEGFR Mutations in Small-Cell Lung Cancers in Patients Who Have Never Smoked
Zakowski, M. F., Ladanyi, M., & Kris, M. G. (2006) · New England Journal of Medicine · doi:10.1056/nejmc053610 · Cited by 254 · see citing works
Self-citationEskens, F. A. L. M., Mom, C. H., Planting, A. S. T., Gietema, J. A., Amelsberg, A., Huisman, H., van Doorn, L., Burger, H., Stopfer, P., Verweij, J., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604108 · Cited by 234 · see citing works
An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors
Chitale, D. A., Gong, Y., Taylor, B. S., Broderick, S., Brennan, C. W., Somwar, R., Golas, B., Wang, L., Motoi, N., Szőke, J., et al. (2009) · Oncogene · doi:10.1038/onc.2009.135 · Cited by 230 · see citing works
Self-citationCappuzzo, F., Ligorio, C., Janne, P. A., Toschi, L., Rossi, E., Trisolini, R., Paioli, D., Tisch, A. H., Magrini, E., Finocchiaro, G., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.09.4300 · Cited by 210 · see citing works
Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling
Shtiegman, K., Kochupurakkal, B. S., Zwang, Y., Pines, G., Starr, A., Vexler, A. M., Citri, A., Katz, M., Lavi, S., Ben-Basat, Y., et al. (2007) · Oncogene · doi:10.1038/sj.onc.1210503 · Cited by 155 · see citing works
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
Self-citationTakezawa, K., Okamoto, I., Nishio, K., Janne, P. A., & Nakagawa, K. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2798 · Cited by 141 · see citing works
Self-citationJanjigian, Y. Y., Azzoli, C. G., Krug, L. M., Pereira, L. K., Rizvi, N. A., Pietanza, M. C., Kris, M. G., Ginsberg, M. S., Pao, W. J., Miller, V. A., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2662 · Cited by 122 · see citing works
Self-citationYonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Engelman, J. A., Varella-Garcia, M., Nakagawa, K., & Janne, P. A. (2011) · European Journal of Cancer · doi:10.1016/s0959-8049(11)72627-2 · Cited by 96 · see citing works
Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma
Politi, K. A., Fan, P., Shen, R., Zakowski, M. F., & VARMUS, H. E. (2009) · Disease Models & Mechanisms · doi:10.1242/dmm.003681 · Cited by 86 · see citing works
Self-citationAntibody-Based Therapy for Solid Tumors
Li, Y., Hsu, K., & Beckman, R. A. (2008) · The Cancer Journal · doi:10.1097/ppo.0b013e318172d71a · Cited by 71 · see citing works
Varella‐Garcia, M., Mitsudomi, T., Yatabe, Y., et al. (2009) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31819667a3 · Cited by 55 · see citing works
Pugh, T. J., Bebb, G. D., Barclay, L., Sutcliffe, M., Fee, J., Salski, C., O'Connor, R. N., Ho, C., Murray, N., Melosky, B. L., et al. (2007) · BMC Cancer · doi:10.1186/1471-2407-7-128 · Cited by 42 · see citing works
Yang, C., Hirsh, V., Cadranel, J. L., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.8062 · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Self-citationCross, 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
Self-citationLindeman, N. I., Cagle, P. T., Beasley, M. B., Chitale, D. A., Dacic, S., Giaccone, G., Jenkins, R. B., Kwiatkowski, D. J., Saldivar, J.-S., Squire, J., et al. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318290868f · Cited by 1,280 · see citing works
Self-citationERBB 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
Checkpoint inhibitors in metastatic EGFR-mutated non–small cell lung cancer-a meta-analysis
Lee, C. K., Man, J., Lord, S., Links, M., Gebski, V., Mok, T., & Yang, J. C.-H. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.10.007 · Cited by 839 · see citing works
Cell death-based treatment of lung adenocarcinoma
Denisenko, T. V., Budkevich, I. N., & Zhivotovsky, B. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0063-y · Cited by 768 · 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
Self-citationEGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance
Uribe, M. L., Marrocco, I., & Yarden, Y. (2021) · Cancers · doi:10.3390/cancers13112748 · Cited by 604 · see citing works
Niederst, 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
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
Epidermal 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
Self-citationLe, X., Puri, S., Negrao, M. V., Nilsson, M. B., Robichaux, J., Boyle, T., Hicks, J. K., Lovinger, K. L., Roarty, E., Rinsurongkawong, W., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1542 · Cited by 387 · 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
Janjigian, Y. Y., Smit, E. F., Groen, H. J. M., Horn, L., Gettinger, S., Camidge, D. R., Riely, G. J., Wang, B., Fu, Y., Chand, V. K., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0326 · Cited by 362 · see citing works
Self-citationHER2 amplification and HER2 mutation are distinct molecular targets in lung cancers
Li, B. T., Ross, D. S., Aisner, D. L., Chaft, J. E., Hsu, M., Kako, S. L., Kris, M. G., Varella-Garcia, M., & Arcila, M. E. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2015.10.025 · Cited by 286 · see citing works
Yu, H. A., Suzawa, K., Jordan, E., Zehir, A., Ni, A., Kim, R., Kris, M. G., Hellmann, M. D., Li, B. T., Somwar, R., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2961 · Cited by 259 · see citing works
Self-citationA Convergence-Based Framework for Cancer Drug Resistance
Konieczkowski, D. J., Johannessen, C. M., & Garraway, L. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.025 · Cited by 258 · see citing works
K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways
Scheffler, M., Ihle, M. A., Hein, R., Merkelbach-Bruse, S., Scheel, A. H., Siemanowski, J., Brägelmann, J., Kron, A., Abedpour, N., Ueckeroth, F., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.12.013 · Cited by 264 · see citing works
Misale, S., Arena, S., Lamba, S., Siravegna, G., Lallo, A., Hobor, S., Russo, M., Buscarino, M., Lazzari, L., Sartore-Bianchi, A., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007947 · Cited by 263 · see citing works
Molecular pathways and therapeutic targets in lung cancer
Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1891 · Cited by 220 · see citing works
“Another mechanism of resistance is amplification of HER2 reported to occur in 12% of tumors that developed resistance to EGFR inhibitors [47].”
BackgroundBlakely, C. M., Pazarentzos, E., Olivas, V., Asthana, S., Yan, J. J., Tan, I., Hrustanovic, G., Chan, E., Lin, L., Neel, D. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.012 · Cited by 204 · 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
Nilsson, M. B., Sun, H., Robichaux, J., Pfeifer, M., McDermott, U., Travers, J., Diao, L., Xi, Y., Tong, P., Shen, L., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz4589 · Cited by 177 · see citing works
Russo, A., Franchina, T., Rita Ricciardi, G. R., Picone, A., Ferraro, G., Zanghì, M., Toscano, G., Giordano, A., & Adamo, V. (2015) · Oncotarget · doi:10.18632/oncotarget.4254 · Cited by 173 · see citing works
Nahar, R., Zhai, W., Zhang, T., Takano, A., Khng, A. J., Lee, Y. Y., Liu, X., Lim, C. H., Koh, T. P. T., Aung, Z. W., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02584-z · Cited by 173 · see citing works
Combinations with Allosteric SHP2 Inhibitor TNO155 to Block Receptor Tyrosine Kinase Signaling
Liu, C., Lu, H., Wang, H., Loo, A., Zhang, X., Yang, G., Kowal, C., Delach, S., Wang, Y., Goldoni, S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2718 · Cited by 167 · see citing works
Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas
Cortot, A. B., & Jänne, P. A. (2014) · European Respiratory Review · doi:10.1183/09059180.00004614 · Cited by 158 · see citing works
Targeting EGFR in Lung Cancer: Current Standards and Developments
Díaz-Serrano, A., Gella, P., Jiménez, E., Zugazagoitia, J., & Paz-Ares Rodríguez, L. (2018) · Drugs · doi:10.1007/s40265-018-0916-4 · Cited by 108 · see citing works
Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma
Neel, D. S., & Bivona, T. G. (2017) · npj Precision Oncology · doi:10.1038/s41698-017-0007-0 · Cited by 98 · see citing works
Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy
Tan, L., Zhang, J., Wang, Y., Wang, X., Wang, Y., Zhang, Z., Shuai, W., Wang, G., Chen, J., Wang, C., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01714 · Cited by 88 · see citing works
Santana-Codina, N., Chandhoke, A. S., Yu, Q., Małachowska, B., Kuljanin, M., Gikandi, A., Stańczak, M., Gableske, S., Jedrychowski, M. P., Scott, D. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.021 · Cited by 77 · see citing works
NSCLC and HER2: between lights and shadows
Ricciardi, G. R. R., Russo, A., Franchina, T., Ferraro, G., Zanghì, M., Picone, A., Scimone, A., & Adamo, V. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000379 · Cited by 78 · see citing works
A genetic interaction analysis identifies cancer drivers that modify EGFR dependency
Liao, S., Davoli, T., Leng, Y., Li, M. Z., Xu, Q., & Elledge, S. J. (2017) · Genes & Development · doi:10.1101/gad.291948.116 · Cited by 67 · see citing works
Genome-wide CRISPR screening reveals genetic modifiers of mutant EGFR dependence in human NSCLC
Zeng, H., Castillo-Cabrera, J., Manser, M., Lu, B., Yang, Z., Strande, V., Begue, D., Zamponi, R., Qiu, S., Sigoillot, F., et al. (2019) · eLife · doi:10.7554/elife.50223 · Cited by 57 · see citing works
Spaans, J. N., & Goss, G. D. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00190 · Cited by 57 · see citing works
Blakely, C. M., & Bivona, T. G. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0387 · Cited by 39 · see citing works
Tsigelny, I. F., Wheler, J. J., Greenberg, J. P., Kouznetsova, V. L., Stewart, D. J., Bazhenova, L., & Kurzrock, R. (2015) · Oncotarget · doi:10.18632/oncotarget.3472 · Cited by 30 · see citing works
Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer
Mendes, C., & Serpa, J. (2019) · Antioxidants · doi:10.3390/antiox8120603 · Cited by 21 · see citing works
- Authors
- Takezawa, K., Pirazzoli, V., Arcila, M. E., Nebhan, C. A., Song, X., de Stanchina, E., Ohashi, K., Janjigian, Y. Y., Spitzler, P. J., Melnick, M. A., Riely, G. J., Kris, M. G., Miller, V. A., Ladanyi, M., Politi, K., & Pao, W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Authors' Affiliations: 1Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee; 2Department of Pathology and Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut; 3Antitumor Assessment Core, Molecular Pharmacology and Chemistry Program, 4Department of Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 5Molecular Diagnostics Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York
- Corresponding author
- Pao, William
- ORCID
- Venue
- Cancer Discovery
- Published
- 2012-10-01
- Volume
- 2
- Issue
- 10
- Pages
- 922-933
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC3473100
- OpenAlex
- W2143913849
- Cited by
- 710
- References
- 37
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 27 · 2023: 37 · 2022: 32 · 2021: 53 · 2020: 71 · 2019: 59 · 2018: 81 · 2017: 65 · 2016: 62 · 2015: 74 · 2014: 60 · 2013: 39 · 2012: 6
- FWCI
- 45.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA121210, P01CA129243, R01CA120247, U54CA143798, R00CA131488, P30CA068485)
- National Institute of General Medical Sciences (T32GM007347)
- 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 Genomics and Diagnostics
- Keywords
- HER2 amplification, acquired drug resistance, EGFR tyrosine kinase inhibitors, EGFR-mutant lung adenocarcinoma, afatinib, cetuximab, T790M mutation, HER2 overexpression, combination therapy, HER2 phosphorylation
- MeSH terms
- Cetuximab, Erlotinib Hydrochloride, Adenocarcinoma of Lung, Afatinib, Adenocarcinoma, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Humans, Lung Neoplasms, Mice, Nude, Mutation, Phosphorylation, Quinazolines, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, Class I Phosphatidylinositol 3-Kinases, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized, 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
