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The quest to overcome resistance to EGFR-targeted therapies in cancer
Open accessAbstract
All patients with metastatic lung, colorectal, pancreatic or head and neck cancers who initially benefit from epidermal growth factor receptor (EGFR)-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the Herculean challenge of killing tumors that are resistant to EGFR inhibitors. Our growing knowledge of resistance pathways provides an opportunity to develop new mechanism-based inhibitors and combination therapies to prevent or overcome therapeutic resistance in tumors. We present a comprehensive review of resistance pathways to EGFR-targeted therapies in lung, colorectal and head and neck cancers and discuss therapeutic strategies that are designed to circumvent resistance.
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Cites
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
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
EGFR 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
Self-citationGefitinib 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
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
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
Erlotinib in Previously Treated Non–Small-Cell Lung Cancer
Shepherd, F. A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E. H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050753 · Cited by 5,419
Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., Bets, D., Mueser, M., Harstrick, A., Verslype, C., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033025 · Cited by 5,035
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
Self-citationMitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., Seto, T., Satouchi, M., Tada, H., Hirashima, T., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70364-x · Cited by 4,090
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Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T., Petrella, F., Spaggiari, L., & Rosell, R. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.9 · Cited by 1,083
Skoulidis, F., Byers, L. A., Diao, L., Papadimitrakopoulou, V. A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E. R., Canales, J. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1236 · Cited by 936
Patient-derived models of acquired resistance can identify effective drug combinations for cancer
Crystal, A. S., Shaw, A. T., Sequist, L. V., Friboulet, L., Niederst, M. J., Lockerman, E. L., Frias, R. L., Gainor, J. F., Amzallag, A., Greninger, P., et al. (2014) · Science · doi:10.1126/science.1254721 · Cited by 708
New horizons in tumor microenvironment biology: challenges and opportunities
Chen, F., Zhuang, X., Lin, L., Yu, P., Wang, Y., Shi, Y., Hu, G., & Sun, Y. (2015) · BMC Medicine · doi:10.1186/s12916-015-0278-7 · Cited by 704
Bauer, R. A. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.05.005 · Cited by 534
Advances in targeted therapy for esophageal cancer
Yang, Y.-M., Hong, P., Xu, W. W., He, Q.-Y., & Li, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00323-3 · Cited by 508
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499
YAP/TAZ Signaling and Resistance to Cancer Therapy
Nguyen, C. D. K., & Yi, C. (2019) · Trends in Cancer · doi:10.1016/j.trecan.2019.02.010 · Cited by 437
Targeting cytokine and chemokine signaling pathways for cancer therapy
Yi, M., Li, T., Niu, M., Zhang, H., Wu, Y., Wu, K., & Dai, Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01868-3 · Cited by 455
Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer
Ruiz-Cordero, R., & Devine, W. P. (2020) · Surgical Pathology Clinics · doi:10.1016/j.path.2019.11.002 · Cited by 448
Unveiling the mechanisms and challenges of cancer drug resistance
Khan, S. U., Fatima, K., Aisha, S., & Malik, F. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01302-1 · Cited by 417
Soria, J.-C., Wu, Y.-L., Nakagawa, K., Kim, S.-W., Yang, J.-J., Ahn, M.-J., Wang, J., Yang, J. C.-H., Lu, Y., Atagi, S., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00121-7 · Cited by 413
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Grommes, C., Pastore, A., Palaskas, N., Tang, S. S., Campos, C., Schartz, D., Codega, P., Nichol, D., Clark, O., Hsieh, W.-Y., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0613 · Cited by 409
Ten things you should know about protein kinases: IUPHAR R eview 14
Fabbro, D., Cowan‐Jacob, S. W., & Moebitz, H. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13096 · Cited by 347
Refining the treatment of NSCLC according to histological and molecular subtypes
Thomas, A., Liu, S. V., Subramaniam, D. S., & Giaccone, G. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.90 · Cited by 321
HER2 Activating Mutations Are Targets for Colorectal Cancer Treatment
Kavuri, S. M., Jain, N., Galimi, F., Cottino, F., Leto, S. M., Migliardi, G., Searleman, A. C., Shen, W., Monsey, J., Trusolino, L., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1211 · Cited by 302
KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target
Román, M., Baraibar, I., López, I., Nadal, E., Rolfo, C., Vicent, S., & Gil-Bazo, I. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0789-x · Cited by 301
Apicella, M., Giannoni, E., Fiore, S., Ferrari, K. J., Fernández-Pérez, D., Isella, C., Granchi, C., Minutolo, F., Sottile, A., Comoglio, P. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.006 · Cited by 299
KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition
Misale, S., Fatherree, J. P., Cortez, E., Li, C., Bilton, S., Timonina, D., Myers, D. T., Lee, D., Gomez-Caraballo, M., Greenberg, M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0368 · Cited by 259
Costa, C., Molina, M. A., Drozdowskyj, A., Giménez-Capitán, A., Bertran-Alamillo, J., Karachaliou, N., Gervais, R., Massuti, B., Wei, J., Moran, T., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2233 · Cited by 229
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
“Several mechanisms have been implicated in resistance to EGFR inhibitors, and they were reviewed recently [35-37].”
BackgroundPeters, S., Zimmermann, S., & Adjei, A. A. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.06.010 · Cited by 155
MET signaling in colon cancer stem-like cells blunts the therapeutic response to EGFR inhibitors.
Luraghi, P., Reato, G., Cipriano, E., Sassi, F., Orzan, F., Bigatto, V., De Bacco, F., Menietti, E., Han, M., Rideout, W. M., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2340-t · Cited by 146
Johnson, G. L., Stuhlmiller, T. J., Angus, S. P., Zawistowski, J. S., & Graves, L. M. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1081 · Cited by 129
Vertical suppression of the EGFR pathway prevents onset of resistance in colorectal cancers
Misale, S., Bozic, I., Tong, J., Peraza-Penton, A., Lallo, A., Baldi, F., Lin, K. H., Truini, M., Trusolino, L., Bertotti, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms9305 · Cited by 122
Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer
Jahanban-Esfahlan, R., Seidi, K., Manjili, M. H., Jahanban-Esfahlan, A., Javaheri, T., & Zare, P. (2019) · Cancers · doi:10.3390/cancers11081207 · Cited by 111
“Meanwhile, EGFR signaling via activation of PI3K/AKT/mTOR and Ras/Raf/ERK axis is another contribution to tumor proliferation [124].”
BackgroundTNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer
Gong, K., Guo, G., Gerber, D. E., Gao, B., Peyton, M., Huang, C., Minna, J. D., Hatanpaa, K. J., Kernstine, K., Cai, L., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96148 · Cited by 98
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
Gong, K., Guo, G., Panchani, N., Bender, M. E., Gerber, D. E., Minna, J. D., Fattah, F., Gao, B., Peyton, M., Kernstine, K., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0048-0 · Cited by 92
Leto, S. M., & Trusolino, L. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1161-2 · Cited by 87
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
Eng, C., Bessudo, A., Hart, L. L., Severtsev, A., Gladkov, O., Müller, L., Kopp, M. V., Vladimirov, V., Langdon, R., Kotiv, B., et al. (2016) · International Journal of Cancer · doi:10.1002/ijc.30049 · Cited by 72
Ansari, M. A., Thiruvengadam, M., Venkidasamy, B., Alomary, M. N., Salawi, A., Chung, I.-M., Shariati, M. A., & Rebezov, M. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.04.005 · Cited by 63
De Angelis, M. L., Zeuner, A., Policicchio, E., Russo, G., Bruselles, A., Signore, M., Vitale, S., De Luca, G., Pilozzi, E., Boe, A., et al. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0214 · Cited by 60
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
Non-small cell lung carcinoma spheroid models in agarose microwells for drug response studies
Luan, Q., Becker, J. H., Macaraniag, C., Massad, M. G., Zhou, J., Shimamura, T., & Papautsky, I. (2022) · Lab on a Chip · doi:10.1039/d2lc00244b · Cited by 45
Bowles, D. W., Kochenderfer, M., Cohn, A., Sideris, L., Nguyen, N., Cline-Burkhardt, V., Schnadig, I., Choi, M., Nabell, L., Chaudhry, A., et al. (2016) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2016.03.004 · Cited by 42
Targeting SALL4 by entinostat in lung cancer
Yong, K. J., Li, A., Ou, W.-B., Hong, C. K. Y., Zhao, W., Wang, F., Tatetsu, H., Yan, B., Qi, L., Fletcher, J. A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12251 · Cited by 41
Li, X., Martinez-Ledesma, E., Zhang, C., Gao, F., Zheng, S., Ding, J., Wu, S., Nguyen, N., Clifford, S. C., Wen, P. Y., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0325 · Cited by 27
Kang, D., Wang, Y., Lin, Y., Ma, W. W., Morgensztern, D., Leventakos, K., Bi, C., Ding, Y., Xiong, J., Yan, M., et al. (2025) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-3691 · Cited by 17
Kirouac, D., Lahdenranta, J., Du, J., Yarar, D., Onsum, M., Nielsen, U., & McDonagh, C. (2015) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.19 · Cited by 5
Abbas, N., Mourad, M., Smaily, H., Al Mahmasani, L., & Shamseddine, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073265 · Cited by 4
Metadata
- Authors
- Chong, C. R., & Jänne, P. A.
- Venue
- Nature Medicine
- Published
- 2013-11
- Volume
- 19
- Issue
- 11
- Pages
- 1389-1400
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2052705131
- Cited by
- 1,052
- References
- 53
- FWCI
- 43.79
- Type
- journal article
- Language
- en
- Open access
- green
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