The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Afatinib restrains K-RAS–driven lung tumorigenesis
Open accessAbstract
K-RAS –mutated lung adenocarcinomas depend on ERBB signaling, and pan-ERBB inhibitors impair K-RAS–driven lung tumorigenesis.
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In the citing paper
“In NSCLCs and CRCs, KRASG12C inhibition leads to an accumulation of activated upstream EGFR and/or other ERBB family members, which facilitates escape from KRASG12C-inhibitor monotherapy110,121–124.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [124]
In the citing paper
“afatinib blocked compensatory ERBB2 and ERBB3 activation, whereas erlotinib and gefitinib did not.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
In the citing paper
“Genetic mouse models revealed that EGFR deletion attenuates mutant KRAS activity and transiently reduces tumor growth.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
In the citing paper
“Notably, both studies revealed a requirement for simultaneous inhibition of multiple ERBB while targeting a single member of the family was not effective.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
In the citing paper
“EGFR inhibition initiated a rapid resistance mechanism involving non-EGFR ERBB family members, which triggered a tumor escape mechanism.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
In the citing paper
“recent studies have challenged this paradigm, which instead demonstrated that the activation of ERBB signaling was required for KRASG12D-driven lung tumorigenesis in preclinical mice models and that pan-ERBB inhibition other than EGFR inhibition alone was strikingly effective to inhibit KRAS-mutant tumor growth and progression (61, 62).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
In the citing paper
“an independent study by Moll et al. demonstrated a requirement for ERBB signaling to support the progression of KRASG12D-driven lung cancer (62).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
In the citing paper
“targeting of MEK alone is frequently hampered by adaptive resistance, which is complex and context-dependent, and can involve activation of various RTKs, including ERBB family, AXL, PDGFR-α, or FGFR1 (26, 53, 59–62).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [62]
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Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Pfaffl, M. W., Tichopad, A., Prgomet, C., & Neuvians, T. P. (2004) · Biotechnology Letters · doi:10.1023/b:bile.0000019559.84305.47 · Cited by 5,065
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
EGFR 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
Easy quantitative assessment of genome editing by sequence trace decomposition
Brinkman, E. K., Chen, T., Amendola, M., & van Steensel, B. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku936 · Cited by 2,390
Heatmapper: web-enabled heat mapping for all
Babicki, S., Arndt, D., Marcu, A., Liang, Y., Grant, J. R., Maciejewski, A., & Wishart, D. S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw419 · Cited by 2,306
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
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997
Wu, Y.-L., Zhou, C., Hu, C.-P., Feng, J., Lu, S., Huang, Y., Li, W., Hou, M., Shi, J. H., Lee, K. Y., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70604-1 · Cited by 1,978
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,927
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517
Alveolar progenitor and stem cells in lung development, renewal and cancer
Desai, T., Brownfield, D., & Krasnow, M. A. (2014) · Nature · doi:10.1038/nature12930 · Cited by 1,062
Jonkers, J., Meuwissen, R. L. J., van der Gulden, H. M. L., Peterse, H. L., van der Valk, M., & Berns, A. J. M. (2001) · Nature Genetics · doi:10.1038/ng747 · Cited by 1,044
Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor
Miettinen, P. J., Berger, J. E., Meneses, J. J., Phung, Y. T., Pedersen, R. A., Werb, Z., & Derynck, R. (1995) · Nature · doi:10.1038/376337a0 · Cited by 1,038
Strain-Dependent Epithelial Defects in Mice Lacking the EGF Receptor
Sibilia, M., & Wagner, E. F. (1995) · Science · doi:10.1126/science.7618085 · Cited by 1,002
Self-citationConditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase
DuPage, M. J. P., Dooley, A. L., & Jacks, T. (2009) · Nature Protocols · doi:10.1038/nprot.2009.95 · Cited by 873
Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state
Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759
Linardou, H., Dahabreh, I. J., Kanaloupiti, D., Siannis, F., Bafaloukos, D., Kosmidis, P., Papadimitriou, C. A., & Murray, S. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70206-7 · Cited by 739
Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism
Lito, P., Solomon, M., Li, L.-S., Hansen, R., & Rosen, N. (2016) · Science · doi:10.1126/science.aad6204 · Cited by 691
Tumor measurement in the nude mouse
Euhus, D., Hudd, C., LaRegina, M. C., & Johnson, F. E. (1986) · Journal of Surgical Oncology · doi:10.1002/jso.2930310402 · Cited by 607
The Differential Effects of Mutant p53 Alleles on Advanced Murine Lung Cancer
Jackson, E. L., Olive, K. P., Tuveson, D. A., Bronson, R., Crowley, D., Brown, M., & Jacks, T. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2193 · Cited by 553
EGF Receptor is Required for KRAS-induced Pancreatic Tumorigenesis
Ardito, C. M., Grüner, B., Takeuchi, K. K., Lubeseder-Martellato, C., Teichmann, N., Mazur, P., DelGiorno, K. E., Carpenter, E. S., Halbrook, C., Hall, J. C., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.07.024 · Cited by 522
Self-citationSurvival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity
Weihua, Z., Tsan, R. Z., Huang, W., Wu, Q., Chiu, C., Fidler, I. J., & Hung, M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.03.015 · Cited by 495
Suppression of lung adenocarcinoma progression by Nkx2-1
Winslow, M. M., Dayton, T. L., Verhaak, R. G. W., Kim-Kiselak, C., Snyder, E. L., Feldser, D. M., Hubbard, D. D., DuPage, M. J., Whittaker, C. A., Hoersch, S., et al. (2011) · Nature · doi:10.1038/nature09881 · Cited by 467
The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase.Preprint
Luetteke, N. C., Phillips, H. K., Qiu, T. H., Copeland, N. G., Earp, H. S., Jenkins, N. A., & Lee, D. C. (1994) · Genes & Development · doi:10.1101/gad.8.4.399 · Cited by 446
EGF Receptor Signaling Is Essential for K-Ras Oncogene-Driven Pancreatic Ductal Adenocarcinoma
Navas, C., Hernández-Porras, I., Schuhmacher, A. J., Sibilia, M., Guerra, C., & Barbacid, M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.001 · Cited by 391
Self-citationTherapeutic Strategies for Targeting Ras Proteins
Gysin, S., Salt, M. B., Young, A. E., & McCormick, F. (2011) · Genes & Cancer · doi:10.1177/1947601911412376 · Cited by 329
The EGF receptor is required for efficient liver regeneration
Natarajan, A., Wagner, B., & Sibilia, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704126104 · Cited by 320
Self-citationMao, C., Qiu, L., Liao, R.-Y., Du, F.-B., Ding, H., Yang, W.-C., Li, J., & Chen, Q. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.11.020 · Cited by 314
Sun, C., Hobor, S., Bertotti, A., Zecchin, D., Huang, S., Galimi, F., Cottino, F., Prahallad, A., Grernrum, W., Tzani, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.045 · Cited by 304
Evidence for type II cells as cells of origin of K-Ras–induced distal lung adenocarcinoma
Xu, X., Rock, J. R., Lu, Y., Futtner, C. R., Schwab, B., Guinney, J., Hogan, B. L. M., & Onaitis, M. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112499109 · Cited by 302
Brugger, W., Triller, N., Błasińska-Morawiec, M., Curescu, S., Sakalauskas, R., Manikhas, G. M., Mazières, J., Whittom, R., Ward, C., Mayne, K., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.8162 · Cited by 284
Clinical Implications of Genomic Discoveries in Lung Cancer
Swanton, C., & Govindan, R. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1504688 · Cited by 274
Papadimitrakopoulou, V. A., Lee, J. J., Wistuba, I. I., Tsao, A. S., Fossella, F. V., Kalhor, N., Gupta, S. K., Byers, L. A., Izzo, J. G., Gettinger, S. N., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.66.0084 · Cited by 182
Identification of cancer initiating cells in K-Ras driven lung adenocarcinoma
Mainardi, S., Mijimolle, N., Francoz, S., Vicente‐Dueñas, C., Sánchez-Garcı́a, I., & Barbacid, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320383110 · Cited by 170
Self-citationChoi, H., Sheng, J., Gao, D., Li, F., Durrans, A., Ryu, S., Lee, S. B., Narula, N., Rafii, S., Elemento, O., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.040 · Cited by 168
An Expression Signature as an Aid to the Histologic Classification of Non–Small Cell Lung Cancer
Girard, L., Rodriguez-Canales, J., Behrens, C., Thompson, D. M., Botros, I. W., Tang, H., Xie, Y., Rekhtman, N., Travis, W. D., Wistuba, I. I., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2900 · Cited by 154
Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis
Grabner, B., Schramek, D., Mueller, K. M., Moll, H. P., Svinka, J., Hoffmann, T., Bauer, E., Blaas, L., Hruschka, N., Zboray, K., et al. (2015) · Nature Communications · doi:10.1038/ncomms7285 · Cited by 146
Self-citationThe ERBB network facilitates KRAS-driven lung tumorigenesis
Kruspig, B., Monteverde, T., Neidler, S., Hock, A., Kerr, E., Nixon, C., Clark, W., Hedley, A., Laing, S., Coffelt, S. B., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao2565 · Cited by 111
Jacobsen, H. J., Poulsen, T. T., Dahlman, A., Kjær, I., Koefoed, K., Sen, J. W., Weilguny, D., Bjerregaard, B., Andersen, C. R., Horak, I. D., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3312 · Cited by 87
Hypophosphorylation of residue Y1045 leads to defective downregulation of EGFRvIII
Han, W., Zhang, T., Yu, H. W., Foulke, J. G., & Tang, C. K. (2006) · Cancer Biology & Therapy · doi:10.4161/cbt.5.10.3226 · Cited by 77
Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial
Rulli, E., Marabese, M., Torri, V., Farina, G., Veronese, S. M., Bettini, A., Longo, F., Moscetti, L. I., Ganzinelli, M., Lauricella, C., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv318 · Cited by 46
Kunii, R., Jiang, S. S., Hasegawa, G., Yamamoto, T., Umezu, H., Watanabe, T., Tsuchida, M., Hashimoto, T., Hamakubo, T., Kodama, T., et al. (2011) · Histopathology · doi:10.1111/j.1365-2559.2011.03764.x · Cited by 43
Ewald, J. A., Wilkinson, J. C., Guyer, C. A., & Staros, J. V. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00014-9 · Cited by 41
Kamata, T., Giblett, S. M., & Pritchard, C. A. (2017) · Blood · doi:10.1182/blood-2017-02-770149 · Cited by 17
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“Previous studies have suggested that key RTKs may play dominant roles in driving adaptive feedback to inhibitors of the MAPK pathway, including EGFR in response to BRAF inhibition in BRAF colorectal cancer and EGFR/HER family kinases or FGFR in response to MEK inhibitors in KRAS-mutant lung cancers (13, 14, 21, 24).”
BackgroundHofmann, M. H., Gmachl, M., Ramharter, J., Savarese, F., Gerlach, D., Marszalek, J. R., Sanderson, M. P., Kessler, D., Trapani, F., Arnhof, H., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0142 · Cited by 444
Metadata
- Authors
- Moll, H. P., Pranz, K., Musteanu, M., Grabner, B., Hruschka, N., Mohrherr, J., Aigner, P., Stiedl, P., Brcic, L., Laszlo, V., Schramek, D., Moriggl, R., Eferl, R., Moldvay, J., Dezso, K., Lopez-Casas, P. P., Stoiber, D., Hidalgo, M., Penninger, J., Sibilia, M., Győrffy, B., Barbacid, M., Dome, B., Popper, H., & Casanova, E.
- Affiliations
- Comprehensive Cancer Center Vienna (AT)
- Ludwig Boltzmann Institute for Cancer Research (AT)
- Spanish National Cancer Research Centre, E-28029 Madrid, Spain.
- Institute of Pathology, Medical University of Graz, AT-8036 Graz, Austria.
- Division of Thoracic Surgery, Department of Surgery and CCC, Medical University of Vienna, AT-1090 Vienna, Austria.
- Institute of Molecular Biotechnology (AT)
- University of Veterinary Medicine Vienna (AT)
- Semmelweis University (HU)
- First Department of Pathology and Experimental Cancer Research, Semmelweis University, HU-1122 Budapest, Hungary.
- Spanish National Cancer Research Centre (ES)
- Medical University of Graz (AT)
- Corresponding author
- Casanova, Emilio
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2018-06-20
- Volume
- 10
- Issue
- 446
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC7610658
- OpenAlex
- W2808999647
- Cited by
- 125
- References
- 51
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 18 · 2021: 21 · 2020: 22 · 2019: 23 · 2018: 9
- FWCI
- 14.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- Austrian Science Fund (FWF-P25599-B19, SFB-F4707, SFB-F06105)
- Fellinger Krebsforschungsverein
- National Research, Development and Innovation Office, Hungary (NVKP_16-1-2016-0037)
- Hungarian NRDI Office (K109626, K108465, KNN121510, SNN114490)
- Hungarian Academy of Science
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- afatinib, KRAS mutation, lung adenocarcinoma, lung carcinogenesis, ErbB signaling, pan-ErbB inhibitor, EGFR, HER2, HER3, ErbB4, tyrosine kinase inhibitors
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Adenocarcinoma of Lung, Afatinib, Humans, Lung Neoplasms, Mutation, Signal Transduction, Proto-Oncogene Proteins p21(ras), Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Proliferation, Carcinogenesis, ErbB Receptors
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