Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer

Linardou, Helena; Dahabreh, Issa J; Kanaloupiti, Dimitra; Siannis, Fotios; Bafaloukos, Dimitrios; Kosmidis, Paris; Papadimitriou, Christos A; Murray, Samuel

doi:10.1016/s1470-2045(08)70206-7

Cited by 739Lung Cancer Treatments and MutationsColorectal Cancer Treatments and StudiesHER2/EGFR in Cancer Research

Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer

Linardou, Helena, Dahabreh, Issa J, Kanaloupiti, Dimitra, Siannis, Fotios, Bafaloukos, Dimitrios, Kosmidis, Paris, Papadimitriou, Christos A, Murray, Samuel·2008·The Lancet Oncology

DOI 10.1016/s1470-2045(08)70206-7

Open this paper in CoChat — free account

Abstract

Background Somatic mutations of the k-RAS oncogene have been assessed as a mechanism of de-novo resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC), and to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). The aim of this systematic review and meta-analysis was to assess if k-RAS mutations represent a candidate predictive biomarker for anti-EGFR-targeted therapeutic strategies in mCRC and NSCLC.Methods We systematically identified articles pertaining to k-RAS mutational status in patients with NSCLC treated with tyrosine-kinase inhibitors (TKI), and patients with mCRC treated with any anti-EGFR-based regimens. Eligible studies had to report complete responses (CR) and partial responses (PR), stratified by k-RAS mutational status. Potential between-study heterogeneity was accommodated by use of random-effects models for bivariable meta-analysis of sensitivity and specificity (the primary endpoints). The positive and negative likelihood ratios (+LR and -LR, respectively) of k-RAS mutations for predicting an absence of response were considered as secondary endpoints and were calculated by use of pooled estimates for sensitivity and specificity.Findings Of 252 retrieved manuscripts, 17 were deemed eligible for the NSCLC meta-analysis (165 of 1008 patients with mutated k-RAS). The presence of k-RAS mutations was significantly associated with an absence of response to TKIs (sensitivity=0.21 [95% CI 0.16-0.28], specificity=0.94 [0.89-0.97]; +LR=3.52; -LR=0.84). Of 68 retrieved manuscripts reporting on anti-EGFR monoclonal-antibody-based treatment of mCRC, eight studies were deemed eligible for the final analysis (306 of 817 patients with mutated k-RAS). The presence of k-RAS mutations was significantly associated with an absence of response to anti-EGFR monoclonal-antibody-based treatments (sensitivity=0.47 [0.43-0.52]; specificity=0.93 [0.83-0.97]; +LR=6.82; -LR=0.57).Interpretation This analysis provides empirical evidence that k-RAS mutations are highly specific negative predictors of response (de-novo resistance) to single-agent EGFR TKIs in advanced NSCLC; and similarly to anti-EGFR monoclonal antibodies alone or in combination with chemotherapy in patients with mCRC. The low sensitivity and relatively high -LR of k-RAS mutations for determining non-responsiveness clearly shows that additional mechanisms of resistance to EGFR inhibitors exist.

Integrity signals

Registry

Crossref · 10.1016/s1470-2045(08)70206-7

Cites

95 of 95 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Mutations within RAS put the RAS protein in a constitutively active state independent of upstream signals driven by growth factor receptor, leading to failure of EGFR-targeted therapies.
“Mutations within RAS put the RAS protein in a constitutively active state independent of upstream signals driven by growth factor receptor [79], leading to the failure of EGFR-targeted therapies.”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [79]

Meta-analysis of Observational Studies in Epidemiology<SUBTITLE>A Proposal for Reporting</SUBTITLE>
Stroup, D. F. (2000) · JAMA · doi:10.1001/jama.283.15.2008 · Cited by 20,623 · see citing works
Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib
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
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 · see citing works
Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework
Biomarkers Definitions Working Group (2001) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2001.113989 · Cited by 6,771 · see citing works
Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement
Moher, D., Cook, D. J., Eastwood, S., Olkin, I., Rennie, D., & Stroup, D. F. (1999) · The Lancet · doi:10.1016/s0140-6736(99)04149-5 · Cited by 4,826 · see citing works
Cancer genes and the pathways they control
Vogelstein, B., & Kinzler, K. W. (2004) · Nature Medicine · doi:10.1038/nm1087 · Cited by 4,245 · see citing works
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group
Moore, M. J., Goldstein, D., Hamm, J., Figer, A., Hecht, J. R., Gallinger, S., Au, H. J., Murawa, P., Walde, D., Wolff, R. A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9525 · Cited by 3,848 · see citing works
Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain
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
Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews
Reitsma, J. B., Glas, A. S., Rutjes, A. W. S., Scholten, R. J. P. M., Bossuyt, P. M., & Zwinderman, A. H. (2005) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.02.022 · Cited by 3,369 · see citing works
ERBB receptors and cancer: the complexity of targeted inhibitors
Hynes, N. E., & Lane, H. A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1609 · Cited by 3,313 · see citing works
Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer
Amado, R. G., Wolf, M., Peeters, M., Van Cutsem, E., Siena, S., Freeman, D. J., Juan, T., Sikorski, R., Suggs, S., Radinsky, R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.7116 · Cited by 3,207 · see citing works
Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Fukuoka, M., Yano, S., Giaccone, G., Tamura, T., Nakagawa, K., Douillard, J., Nishiwaki, Y., Vansteenkiste, J., Kudoh, S., Rischin, D., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.10.038 · Cited by 2,871 · see citing works
Efficacy of Gefitinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in Symptomatic Patients With Non–Small Cell Lung Cancer: A Randomized Trial
Kris, M. G., Natale, R. B., Herbst, R. S., Lynch, Jr., Prager, D., Belani, C. P., Schiller, J. H., Kelly, K., Spiridonidis, H., Sandler, A., et al. (2003) · JAMA · doi:10.1001/jama.290.16.2149 · Cited by 2,517 · see citing works
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Lièvre, A., Bachet, J.-B., Le Corre, D., Boige, V., Landi, B., Emile, J.-F., Côté, J.-F., Tomasic, G., Penna, C., Ducreux, M., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0191 · Cited by 2,229 · see citing works
EGFR and cancer prognosis.
Nicholson, R., Gee, J., & Harper, M. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00231-3 · Cited by 2,132 · see citing works
EGFR Antagonists in Cancer Treatment
Ciardiello, F., & Tortora, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707704 · Cited by 2,063 · see citing works
Epidermal growth factor receptor (EGFR) signaling in cancer
Normanno, N., Luca, A. D., Bianco, C., Strizzi, L., Mancino, M., Maiello, M. R., Carotenuto, A., Feo, G. D., Caponigro, F., & Salomon, D. S. (2005) · Gene · doi:10.1016/j.gene.2005.10.018 · Cited by 2,035 · see citing works
Gefitinib in Combination With Gemcitabine and Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 1
Giaccone, G., Herbst, R. S., Manegold, C., Scagliotti, G. V., Rosell, R., Miller, V. A., Natale, R. B., Schiller, J. H., von Pawel, J., Pluzanska, A., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.001 · Cited by 1,712 · see citing works
Gefitinib in Combination With Paclitaxel and Carboplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 2
Herbst, R. S., Giaccone, G., Schiller, J. H., Natale, R. B., Miller, V. A., Manegold, C., Scagliotti, G. V., Rosell, R., Oliff, I. A., Reeves, J. A., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.07.215 · Cited by 1,703 · see citing works
Diagnostic tests 4: likelihood ratios
Deeks, J. J., & Altman, D. G. (2004) · BMJ · doi:10.1136/bmj.329.7458.168 · Cited by 1,600 · see citing works
Epidermal growth factor receptor: Mechanisms of activation and signalling
Jorissen, R. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00098-8 · Cited by 1,565 · see citing works
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 · see citing works
KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab
Lièvre, A., Bachet, J., Boige, V., Cayre, A., Corre, D. L., Buc, E., Ychou, M., Bouché, O., Landi, B., Louvet, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.5906 · Cited by 1,456 · see citing works
Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib
Eberhard, D. A., Johnson, B. E., Amler, L. C., Goddard, A. D., Heldens, S., Herbst, R. S., Ince, W. L., Janne, P. A., Januario, T., Johnson, D. H., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.857 · Cited by 1,453 · see citing works
Systematic reviews of evaluations of diagnostic and screening tests
Deeks, J. J. (2001) · BMJ · doi:10.1136/bmj.323.7305.157 · Cited by 1,345 · see citing works
RAF/RAS oncogenes and mismatch-repair status
Rajagopalan, H., Bardelli, A., Lengauer, C., Kinzler, K. W., Vogelstein, B., & Velculescu, V. E. (2002) · Nature · doi:10.1038/418934a · Cited by 1,224 · see citing works
Expression of Epiregulin and Amphiregulin and K-ras Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab
Khambata-Ford, S., Garrett, C. R., Meropol, N. J., Basik, M., Harbison, C. T., Wu, S., Wong, T. W., Huang, X., Takimoto, C. H., Godwin, A. K., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.10.5437 · Cited by 1,125 · see citing works
Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study
Moroni, M., Veronese, S., Benvenuti, S., Marrapese, G., Sartore-Bianchi, A., Di Nicolantonio, F., Gambacorta, M., Siena, S., & Bardelli, A. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70102-9 · Cited by 941 · see citing works
Systematic reviews of evaluations of diagnostic and screening tests
(2001) · Europe PMC (PubMed Central) · Cited by 850 · see citing works
Oncogenic Activation of the RAS/RAF Signaling Pathway Impairs the Response of Metastatic Colorectal Cancers to Anti–Epidermal Growth Factor Receptor Antibody Therapies
Benvenuti, S., Sartore-Bianchi, A., Di Nicolantonio, F., Zanon, C., Moroni, M., Veronese, S., Siena, S., & Bardelli, A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4158 · Cited by 830 · see citing works
KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab
De Roock, W., Piessevaux, H., De Schutter, J., Janssens, M., De Hertogh, G., Personeni, N., Biesmans, B., Van Laethem, J.-L., Peeters, M., Humblet, Y., et al. (2008) · Annals of Oncology · doi:10.1093/annonc/mdm496 · Cited by 827 · see citing works
A unification of models for meta-analysis of diagnostic accuracy studies
Harbord, R. M., Deeks, J. J., Egger, M., Whiting, P. F., & Sterne, J. A. C. (2006) · Biostatistics · doi:10.1093/biostatistics/kxl004 · Cited by 753 · see citing works
Tumor Marker Utility Grading System: a Framework to Evaluate Clinical Utility of Tumor Markers
Hayes, D. F., Bast, R. C., Desch, C. E., Fritsche, H. A., Kemeny, N. E., Jessup, J. M., Locker, G. Y., Macdonald, J. S., Mennel, R. G., Norton, L., et al. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.20.1456 · Cited by 746 · see citing works
Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy
Di Fiore, F., Blanchard, F., Charbonnier, F., Le Pessot, F., Lamy, A., Galais, M. P., Bastit, L., Killian, A., Sesboüé, R., Tuech, J. J., et al. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603685 · Cited by 734 · see citing works
Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer
Hirsch, F. R., Varella-Garcia, M., Bunn, P. A., Franklin, W. A., Dziadziuszko, R., Thatcher, N., Chang, A., Parikh, P., Pereira, J. R., Ciuleanu, T., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.3958 · Cited by 703 · see citing works
Epidermal Growth Factor Receptor Targeting in Cancer
Mendelsohn, J. M., & Baselga, J. M. (2006) · Seminars in Oncology · doi:10.1053/j.seminoncol.2006.04.003 · Cited by 693 · see citing works
Epidermal Growth Factor Receptor Mutations, Small-Molecule Kinase Inhibitors, and Non–Small-Cell Lung Cancer: Current Knowledge and Future Directions
Pao, W. J., & Miller, V. A. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.799 · Cited by 628 · see citing works
Epidermal Growth Factor Receptor Mutations and Gene Amplification in Non–Small-Cell Lung Cancer: Molecular Analysis of the IDEAL/INTACT Gefitinib Trials
Bell, D. W., Lynch, T. J., Haserlat, S. M., Harris, P. L., Okimoto, R. A., Brannigan, B. W., Sgroi, D. C., Muir, B., Riemenschneider, M. J., Iacona, R. B., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.7078 · Cited by 598 · see citing works
Analysis of Epidermal Growth Factor Receptor Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib
Kosaka, T., Yatabe, Y., Endoh, H., Yoshida, K., Hida, T., Tsuboi, M., Tada, H., Kuwano, H., & Mitsudomi, T. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0714 · Cited by 595 · see citing works
KRASMutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Massarelli, E., Varella‐Garcia, M., Tang, X., Xavier, A. C., Ozburn, N. C., Liu, D. D., Bekele, B. N., Herbst, R. S., & Wistuba, I. I. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3043 · Cited by 594 · see citing works
We should desist using RECIST, at least in GIST.
Benjamin, R., Choi, H., Macapinlac, H., Burgess, M., Patel, S. R., Chen, L. L., Podoloff, D., & Charnsangavej, C. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.3411 · Cited by 570 · see citing works
PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients
Frattini, M., Saletti, P., Romagnani, E., Martin, V, Molinari, F., Ghisletta, M., Camponovo, A., Etienne, L. L., Cavalli, F., & Mazzucchelli, L. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6604009 · Cited by 540 · see citing works
Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis
Buyse, M. E., Thirion, P. G., Carlson, R. W., Burzykowski, T., Molenberghs, G., & Piedbois, P. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02528-9 · Cited by 425 · see citing works
Gefitinib — a novel targeted approach to treating cancer
Herbst, R. S., Fukuoka, M., & Baselga, J. M. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1506 · Cited by 401 · see citing works
KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience
Cutsem, E. V., Láng, I., D’Haens, G., Moiseyenko, V. M., Załuski, J., Folprecht, G., Tejpar, S., Kisker, O., Stroh, C., & Rougier, P. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.2 · Cited by 372 · see citing works
Prognostic versus predictive value of biomarkers in oncology
Oldenhuis, C. N. A. M., Oosting, S. F., Gietema, J. A., & de Vries, E. G. E. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.03.006 · Cited by 349 · see citing works
Similarities and Differences
Diamond, G., Beckloff, N., Ryan, L. K., Res, J. D., Diamond, G., Beckloff, N., & Ryan, L. K. (2005) · SAGE Publications Ltd eBooks · doi:10.4135/9781849208765.n5 · Cited by 339 · see citing works
Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer
Jackman, D. M., Yeap, B. Y., Lindeman, N. I., Fidias, P., Rabin, M. S., Temel, J. S., Skarin, A. T., Meyerson, M. M., Tisch, A. H., Borras, A. M., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.5754 · Cited by 304 · see citing works
Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Miller, V. A., Riely, G. J., Zakowski, M. F., Li, A. R., Patel, J. D., Heelan, R. T., Kris, M. G., Sandler, A. B., Carbone, D. P., Tsao, A. S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.0062 · Cited by 295 · see citing works
EGFR Targeting of Solid Tumors
Rocha‐Lima, C., Soares, H. P., Raez, L. E., & Singal, R. (2007) · Cancer Control · doi:10.1177/107327480701400313 · Cited by 275 · see citing works
Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib
Hirsch, F. R., Varella‐Garcia, M., Cappuzzo, F., McCoy, J., Bemis, L., Xavier, A. C., Dziadziuszko, R., Gumerlock, P. H., Chansky, K., West, H., et al. (2007) · Annals of Oncology · doi:10.1093/annonc/mdm003 · Cited by 266 · see citing works
Optimization of Patient Selection for Gefitinib in Non–Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation
Han, S., Kim, T., Jeon, Y. K., Hwang, P. G., Im, S., Lee, K.-H., Kim, J. H., Kim, D., Heo, D. S., Kim, N. K., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2845 · Cited by 250 · see citing works
Evaluating the Potential Usefulness of New Prognostic and Predictive Indicators on Node-Negative Breast Cancer Patients
Gasparini, G., Pozza, F., & Harris, A. L. (1993) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/85.15.1206 · Cited by 244 · see citing works
KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience
Bokemeyer, C., Bondarenko, I., Hartmann, J. T., de Braud, F., Volovat, C. D., Nippgen, J., Stroh, C., Celik, I., & Koralewski, P. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.4000 · Cited by 240 · see citing works
FDA Drug Approval Summary: Panitumumab (Vectibix™)
Giusti, R. M., Shastri, K. A., Cohen, M. H., Keegan, P., & Pazdur, R. (2007) · The Oncologist · doi:10.1634/theoncologist.12-5-577 · Cited by 215 · see citing works
Prospective Study of Gefitinib in Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization–Positive/Phospho-Akt–Positive or Never Smoker Patients With Advanced Non–Small-Cell Lung Cancer: The ONCOBELL Trial
Cappuzzo, 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
Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study
Andreyev, J. N., Norman, A. R., Cunningham, D., Oates, J. R., Dix, B. R., Iacopetta, B. J., Young, J. P., Walsh, T. P., Ward, R. L., Hawkins, N., et al. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1964 · Cited by 204 · see citing works
Erlotinib for Frontline Treatment of Advanced Non–Small Cell Lung Cancer: a Phase II Study
Giaccone, G., Ruiz, M. I. G., Chevalier, T. L., Thatcher, N., Smit, E. F., Rodríguez, J. A., Janne, P. A., Oulid-Aïssa, D., & Soria, J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0260 · Cited by 199 · see citing works
Disease Control Rate at 8 Weeks Predicts Clinical Benefit in Advanced Non–Small-Cell Lung Cancer: Results From Southwest Oncology Group Randomized Trials
Lara, P. N., Redman, M. W., Kelly, K. L., Edelman, M. J., Williamson, S. K., Crowley, J. J., & Gandara, D. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.0344 · Cited by 182 · see citing works
Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis
Johnson, K. R., Ringland, C. L., Stokes, B., Anthony, D., Freemantle, N., Irs, A., Hill, S. R., & Ward, R. L. (2006) · The Lancet Oncology · doi:10.1016/s1470-2045(06)70800-2 · Cited by 176 · see citing works
Somatic Mutations of the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor and Tyrosine Kinase Inhibitor Response to TKIs in Non-small Cell Lung Cancer: An Analytical Database
Murray, S. J., Dahabreh, I. J., Linardou, H., Manoloukos, M., Bafaloukos, D. I., & Kosmidis, P. (2008) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31818071f3 · Cited by 153 · see citing works
Self-citation
EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer
van Zandwijk, N., Mathy, A., Boerrigter, L., Ruijter, H. J., Tielen, I. H. G., de Jong, D., Baas, P., Burgers, S. A., & Nederlof, P. M. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl323 · Cited by 146 · see citing works
High Expression of ErbB Family Members and Their Ligands in Lung Adenocarcinomas That Are Sensitive to Inhibition of Epidermal Growth Factor Receptor
Fujimoto, N., Wislez, M., Zhang, J., Iwanaga, K., Dackor, J., Hanna, A. E., Kalyankrishna, S., CODY, D. D., Price, R. E., Sato, M., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1977 · Cited by 146 · see citing works
EGFR targeting therapies: Monoclonal antibodies versus tyrosine kinase inhibitors
Dassonville, O., Bozec, A., Fischel, J. L., & Milano, G. A. (2007) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2006.12.008 · Cited by 131 · see citing works
Clinicopathologic Significance of the Mutations of theEpidermal Growth Factor ReceptorGene in Patients with Non–Small Cell Lung Cancer
Tomizawa, Y., Iijima, H., Sunaga, N., Sato, K., Takise, A., Otani, Y., Tanaka, S., Suga, T., Saito, R., Ishizuka, T., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0441 · Cited by 130 · see citing works
The impact of epidermal growth factor receptor gene status on gefitinib‐treated Japanese patients with non‐small‐cell lung cancer
Ichihara, S., Toyooka, S., Fujiwara, Y., Hotta, K., Shigematsu, H., Tokumo, M., Soh, J., Asano, H., Ichimura, K., Aoe, K., et al. (2006) · International Journal of Cancer · doi:10.1002/ijc.22513 · Cited by 119 · see citing works
Radiotherapy versus carboplatin for stage I seminoma: Updated analysis of the MRC/EORTC randomized trial (ISRCTN27163214)
Oliver, R. T. D., Mead, G. M., Fogarty, P. J., & Stenning, S. P. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.1 · Cited by 98 · see citing works
Current situation of Panitumumab, Matuzumab, Nimotuzumab and Zalutumumab
Rivera, F., Vega-Villegas, M. E., López-Brea, M., et al. (2007) · Acta Oncologica · doi:10.1080/02841860701704724 · Cited by 89 · see citing works
Role of cMET expression in non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors
Zucali, P. A., Ruiz, M. I. G., Giovannetti, E., Destro, A., Varella‐Garcia, M., Floor, K., Ceresoli, G. L., Rodríguez, J. A., Garassino, I. M. G., Comoglio, P. M., et al. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn240 · Cited by 89 · see citing works
Microvessel density as a prognostic factor in non-small-cell lung carcinoma: a meta-analysis of individual patient data
Trivella, M., Pezzella, F., Pastorino, U., Harris, A. L., & Altman, D. G. (2007) · The Lancet Oncology · doi:10.1016/s1470-2045(07)70145-6 · Cited by 83 · see citing works
PTEN and PIK3CA Expression Is Associated with Prolonged Survival after Gefitinib Treatment in EGFR-Mutated Lung Cancer Patients
Endoh, H., Yatabe, Y., Kosaka, T., Kuwano, H., & Mitsudomi, T. (2006) · Journal of Thoracic Oncology · doi:10.1016/s1556-0864(15)30374-9 · Cited by 82 · see citing works
Determinants of RASistance to Anti–Epidermal Growth Factor Receptor Agents
Baselga, J. M., & Rosen, N. X. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.3700 · Cited by 75 · see citing works
Small Molecules with EGFR-TK Inhibitor Activity
Albanell, J., & Gascón, P. (2005) · Current Drug Targets · doi:10.2174/1389450053765888 · Cited by 69 · see citing works
Graphical presentation of diagnostic information
Whiting, P. F., Sterne, J. A. C., Westwood, M. E., Bachmann, L. M., Harbord, R. M., Egger, M., & Deeks, J. J. (2008) · BMC Medical Research Methodology · doi:10.1186/1471-2288-8-20 · Cited by 61 · see citing works
Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer
Sasaki, H., Endo, K., Okuda, K., et al. (2007) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-007-0320-z · Cited by 61 · see citing works
Novel approaches to treatment of advanced colorectal cancer with anti‐EGFR monoclonal antibodies
Zhang, W., Gordon, M. A., & Lenz, H. (2006) · Annals of Medicine · doi:10.1080/09546630601070812 · Cited by 54 · see citing works
Dual Inhibition of the Epidermal Growth Factor Receptor with Cetuximab, an IgG1 Monoclonal Antibody, and Gefitinib, A Tyrosine Kinase Inhibitor, in Patients with Refractory Non-small Cell Lung Cancer (NSCLC): A Phase I Study
Ramalingam, S. S., Forster, J., Naret, C., Evans, T. L., Sulecki, M., Lu, H., Teegarden, P., Weber, M. R., & Belani, C. P. (2008) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181653d1b · Cited by 51 · see citing works
Mutational analysis of gene families in human cancer
Bardelli, A., & Velculescu, V. E. (2004) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.12.009 · Cited by 47 · see citing works
Increased epidermal growth factor receptor (EGFR) gene copy number is strongly associated with EGFR mutations and adenocarcinoma in non-small cell lung cancers: A chromogenic in situ hybridization study of 182 patients
Chang, J. W., Liu, H.-P., Hsieh, M., Fang, Y., Hsieh, M., Hsieh, J., Chiu, Y.-T., Tsai, H., Chen, Y., Chen, Y., et al. (2008) · Lung Cancer · doi:10.1016/j.lungcan.2008.01.009 · Cited by 45 · see citing works
PTEN and PIK3CA Expression Is Associated with Prolonged Survival after Gefitinib Treatment in EGFR-Mutated Lung Cancer Patients
Endoh, H., Yatabe, Y., Kosaka, T., et al. (2006) · Journal of Thoracic Oncology · doi:10.1097/01243894-200609000-00006 · Cited by 40 · see citing works
Mutations of epidermal growth factor receptor of non-small cell lung cancer were associated with sensitivity to gefitinib in recurrence after surgery
Kondo, M., Yokoyama, T., Fukui, T., Yoshioka, H., Yokoi, K., Nagasaka, T., Imaizumi, K., Kume, H., Hasegawa, Y., Shimokata, K., et al. (2005) · Lung Cancer · doi:10.1016/j.lungcan.2005.06.008 · Cited by 38 · see citing works
Economic impact of gefitinib for refractory non-small-cell lung cancer: a Markov model-based analysis
CHOUAID, C., Monnet, I., Robinet, G., et al. (2007) · Current Medical Research and Opinion · doi:10.1185/030079907x199718 · Cited by 34 · see citing works
Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer
Adams, R., & Maughan, T. (2007) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.7.4.503 · Cited by 32 · see citing works
Epidermal Growth Factor Receptor Inhibitors in Lung Cancer: Smaller or Larger Molecules, Selected or Unselected Populations?
Hirsch, F. R., & Bunn, P. A. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.6129 · Cited by 26 · see citing works
Cetuximab in the Treatment of Metastatic Colorectal Cancer: a Model-Based Cost-Effectiveness Analysis
Norum, J. (2006) · Journal of Chemotherapy · doi:10.1179/joc.2006.18.5.532 · Cited by 23 · see citing works
siRNA Targeting against EGFR, a Promising Candidate for a Novel Therapeutic Application to Lung Adenocarcinoma
Yamanaka, S., Gu, Z., Sato, M., Fujisaki, R., Inomata, K., Sakurada, A., Inoue, A., Nukiwa, T., Kondo, T., & Horii, A. (2008) · Pathobiology · doi:10.1159/000113789 · Cited by 23 · see citing works
Cetuximab in the treatment of metastatic colorectal cancer
Moosmann, N., & Heinemann, V. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.2.243 · Cited by 21 · see citing works
The relationship of K-ras mutations and EGFR gene copy number to outcome in patients treated with Erlotinib on National Cancer Institute of Canada Clinical Trials Group trial study PA.3
Moore, M. J., Santos, G. D. C., Kamel‐Reid, S., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.25.18_suppl.4521 · Cited by 21 · see citing works
A systematic review of economic analyses of pharmaceutical therapies for advanced colorectal cancer
Krol, M., Koopman, M., Groot, C. A. U., et al. (2007) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.8.9.1313 · Cited by 20 · see citing works
Managing Dermatologic Toxicities of Epidermal Growth Factor Receptor Inhibitors
Chou, L. S., Garey, J. S., Oishi, K., et al. (2006) · Clinical Lung Cancer · doi:10.3816/clc.2006.s.009 · Cited by 17 · see citing works
Buccal Mucosa Cells as In vivo Model to Evaluate Gefitinib Activity in Patients with Advanced Non–Small Cell Lung Cancer
Loprevite, M., Tiseo, M., Chiaramondia, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0805 · Cited by 17 · see citing works
EGFR mutation status and prognosis for gefitinib treatment in Japanese lung cancer
Sasaki, H., Endo, K., Mizuno, K., Yano, M., Fukai, I., Yamakawa, Y., & Fujii, Y. (2005) · Lung Cancer · doi:10.1016/j.lungcan.2005.09.004 · Cited by 15 · see citing works
Molecular Selection of Patients for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer With Epidermal Growth Factor Inhibitors: Not Quite Ready for Prime Time
Shepherd, F. A. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.4286 · Cited by 12 · see citing works
Microvessel density as a prognostic factor in non-small-cell lung carcinoma: a meta-analysis of individual patient data (vol 8, pg 488, 2007)
Trivella, M., Pezzella, F., Pastorino, U., et al. (2007) · The Lancet Oncology · Cited by 11 · see citing works
[Mutational analysis of EGFR and K-RAS in Chinese patients with non-small cell lung cancer].
Liu, F., Jiang, B., Sheng-ji, G., et al. (2007) · PubMed · Cited by 7 · see citing works

Flagged first, then by citations

Sorted by citations

Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy
Yu, T., Guo, F., Yu, Y., Sun, T., Ma, D., Han, J., Qian, Y., Kryczek, I., Sun, D., Nagarsheth, N., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.008 · Cited by 2,198 · see citing works
RAS-targeted therapies: is the undruggable drugged?
Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103 · 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
Molecular Mechanisms of Resistance to Cetuximab and Panitumumab in Colorectal Cancer
Bardelli, A., & Siena, S. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.6116 · Cited by 746 · see citing works
Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer
Laurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6796 · Cited by 673 · see citing works
Epidermal growth factor receptor targeting in cancer: a review of trends and strategies
Yewale, C., Baradia, D., Vhora, I., Patil, S., & Misra, A. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.07.100 · Cited by 533 · see citing works
Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS -Mutant Non–Small Cell Lung Cancer
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1841 · Cited by 466 · see citing works
Implications for KRAS status and EGFR-targeted therapies in metastatic CRC
Normanno, N., Tejpar, S., Morgillo, F., De Luca, A., Van Cutsem, E., & Ciardiello, F. (2009) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.111 · Cited by 436 · see citing works
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 · see citing works
Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer
Sartore-Bianchi, A., Di Nicolantonio, F., Nichelatti, M., Molinari, F., De Dosso, S., Saletti, P., Martini, M., Cipani, T., Marrapese, G., Mazzucchelli, L., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007287 · Cited by 259 · see citing works
Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies
Zhou, J., Ji, Q., & Li, Q. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02130-2 · Cited by 246 · 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
Targeting EGFR L858R/T790M and EGFR L858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry
Lu, X., Yu, L., Zhang, Z., Ren, X., Smaill, J. B., & Ding, K. (2018) · Medicinal Research Reviews · doi:10.1002/med.21488 · Cited by 173 · see citing works
Increased Detection Sensitivity for KRAS Mutations Enhances the Prediction of Anti-EGFR Monoclonal Antibody Resistance in Metastatic Colorectal Cancer
Molinari, F., Felicioni, L., Buscarino, M., De Dosso, S., Buttitta, F., Malatesta, S., Movilia, A., Luoni, M., Boldorini, R., Alabiso, O., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3137 · Cited by 159 · see citing works
A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors
Loboda, A., Nebozhyn, M., Klinghoffer, R., Frazier, J., Chastain, M., Arthur, W., Roberts, B., Zhang, T., Chenard, M., Haines, B., et al. (2010) · BMC Medical Genomics · doi:10.1186/1755-8794-3-26 · Cited by 152 · see citing works
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors vs Conventional Chemotherapy in Non–Small Cell Lung Cancer Harboring Wild-Type Epidermal Growth Factor Receptor: A Meta-analysis
Lee, J.-K., Hahn, S., Kim, D.-W., Suh, K. J., Keam, B., Kim, T. M., Lee, S.-H., & Heo, D. S. (2014) · JAMA · doi:10.1001/jama.2014.3314 · Cited by 141 · see citing works
Afatinib restrains K-RAS–driven lung tumorigenesis
Moll, H. P., Pranz, K., Musteanu, M., Grabner, B., Hruschka, N., Mohrherr, J., Aigner, P., Stiedl, P., Brcic, L., Laszlo, V., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao2301 · Cited by 125 · see citing works
Current therapy of KRAS-mutant lung cancer
Ghimessy, A., Radeczky, P., Laszlo, V., Hegedus, B., Renyi-Vamos, F., Fillinger, J., Klepetko, W., Lang, C., Dome, B., & Megyesfalvi, Z. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09903-9 · Cited by 115 · see citing works
Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance
Li, Q.-H., Wang, Y.-Z., Tu, J., Liu, C.-W., Yuan, Y.-J., Lin, R., He, W.-L., Cai, S.-R., He, Y.-L., & Ye, J.-N. (2020) · Gastroenterology Report · doi:10.1093/gastro/goaa026 · Cited by 119 · see citing works
Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study
Karampeazis, A., Voutsina, A., Souglakos, J., Kentepozidis, N., Giassas, S., Christofillakis, C., Kotsakis, A., Papakotoulas, P., Rapti, A., Agelidou, M., et al. (2013) · Cancer · doi:10.1002/cncr.28132 · Cited by 113 · see citing works
KRAS Protein Stability Is Regulated through SMURF2: UBCH5 Complex-Mediated β-TrCP1 Degradation
Shukla, S., Allam, U. S., Ahsan, A., Chen, G., Krishnamurthy, P. M., Marsh, K., Rumschlag, M., Shankar, S., Whitehead, C., Schipper, M., et al. (2014) · Neoplasia · doi:10.1593/neo.14184 · Cited by 96 · see citing works
KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy
Guan, J.-L., Zhong, W.-Z., An, S.-J., Yang, J.-J., Su, J., Chen, Z.-H., Yan, H.-H., Chen, Z.-Y., Huang, Z.-M., Zhang, X.-C., et al. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2754-z · Cited by 87 · see citing works
Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases
Mak, K. S., Gainor, J. F., Niemierko, A., Oh, K. S., Willers, H., Choi, N. C., Loeffler, J. S., Sequist, L. V., Shaw, A. T., & Shih, H. A. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nou146 · Cited by 83 · see citing works
Identification of mutant K-Ras-dependent phenotypes using a panel of isogenic cell lines
Vartanian, S., Bentley, C., Brauer, M. J., Li, L., Shirasawa, S., Sasazuki, T., Kim, J.-S., Haverty, P., Stawiski, E., Modrusan, Z., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.394130 · Cited by 65 · see citing works
Pooled analysis of the prognostic and predictive value of KRAS mutation status and mutation subtype in patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors
Zer, A., Ding, K., Lee, S. M., Goss, G. D., Seymour, L., Ellis, P. M., Hackshaw, A., Bradbury, P. A., Han, L., O’Callaghan, C. J., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2015.11.010 · Cited by 56 · see citing works
Toll-like Receptor 9 Agonist IMO Cooperates with Cetuximab in K - Ras Mutant Colorectal and Pancreatic Cancers
Rosa, R., Melisi, D., Damiano, V., Bianco, R., Garofalo, S., Gelardi, T., Agrawal, S., Di Nicolantonio, F., Scarpa, A., Bardelli, A., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3376 · Cited by 54 · see citing works
A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER
Goldman, J. W., Mazieres, J., Barlesi, F., Dragnev, K. H., Koczywas, M., Göskel, T., Cortot, A. B., Girard, N., Wesseler, C., Bischoff, H., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.578756 · Cited by 52 · see citing works
Synthetic lethality of glutaminolysis inhibition, autophagy inactivation and asparagine depletion in colon cancer
Li, J., Song, P., Zhu, L., Aziz, N., Zhou, Q., Zhang, Y., Xu, W., Feng, L., Chen, D., Wang, X., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16844 · Cited by 46 · see citing works
Stem cell property epithelial‐to‐mesenchymal transition is a core transcriptional network for predicting cetuximab (Erbitux™) efficacy in KRAS wild‐type tumor cells
Oliveras‐Ferraros, C., Vazquez‐Martin, A., Cufí, S., Queralt, B., Báez, L., Guardeño, R., Hernández‐Yagüe, X., Martin‐Castillo, B., Brunet, J., & Menendez, J. A. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22952 · Cited by 47 · see citing works
Outcomes of First-Generation EGFR-TKIs Against Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Post Hoc Analysis of the BE-POSITIVE Study
Pilotto, S., Rossi, A., Vavalà, T., Follador, A., Tiseo, M., Galetta, D., Morabito, A., Di Maio, M., Martelli, O., Caffo, O., et al. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2017.05.016 · Cited by 46 · see citing works

Early and late gene expression programs in developing somatic cells of Volvox carteri
Tam, L.-W., Stamer, K. A., & Kirk, D. L. (1991) · Developmental Biology · doi:10.1016/0012-1606(91)90213-m · Cited by 20 · see citing works
HETEROGENEOUS EXPRESSION OF ONCOGENES IN SMALL-CELL LUNG-CANCER XENOGRAFTS
Arvelo, F. A., Poupon, M., Baldeyrou, P., et al. (1993) · International Journal of Oncology · doi:10.3892/ijo.2.4.621 · Cited by 4 · see citing works
Germinal and somatic cell interrelationships in gonadal sex differentiation
Wai‐Sum, O., & Baker, T. G. (1978) · annales de biologie animale biochimie biophysique · doi:10.1051/rnd:19780304 · Cited by 19 · see citing works
[Segregation of the somatic and germ-cell pathways of development in Drosophila].
Ivanov, A. I. (1990) · PubMed
Advances in EGFR-targeted therapy of non-small cell lung cancer
Sun, P. (2017) · Chinese Journal of Asthma · doi:10.3760/cma.j.issn.1673-436x.2017.02.014

Authors: Linardou, H., Dahabreh, I. J., Kanaloupiti, D., Siannis, F., Bafaloukos, D., Kosmidis, P., Papadimitriou, C. A., & Murray, S.
Affiliations: Metropolitan Hospital (GR)
National and Kapodistrian University of Athens (GR)
Hygeia Hospital (GR)
Corresponding author: Murray, Samuel
ORCID: Linardou, Helena
Dahabreh, Issa J
Siannis, Fotios
Kosmidis, Paris
Papadimitriou, Christos A
Murray, Samuel
Venue: The Lancet Oncology
Publisher: Elsevier BV
Published: 2008-10
Volume: 9
Issue: 10
Pages: 962-972
ISSN: 1470-2045 (ISSN-L)
DOI: 10.1016/s1470-2045(08)70206-7
OpenAlex: W2128059540
Cited by: 739
References: 95
Citations by year: 2026: 8 · 2025: 11 · 2024: 11 · 2023: 21 · 2022: 15 · 2021: 23 · 2020: 23 · 2019: 16 · 2018: 29 · 2017: 46 · 2016: 56 · 2015: 53 · 2014: 71 · 2013: 68 · 2012: 84
FWCI: 10.71
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: The Lancet Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords: KRAS mutation, anti-EGFR therapy, drug resistance, predictive biomarkers, non-small cell lung cancer, metastatic colorectal cancer, tyrosine kinase inhibitors, anti-EGFR monoclonal antibody, treatment response, sensitivity and specificity, likelihood ratios, advanced cancer, predictive biomarker validation, EGFR tyrosine kinase inhibitor resistance, anti-EGFR antibody resistance
MeSH terms: Antibodies, Monoclonal, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Colonic Neoplasms, Genetic Markers, Humans, Lung Neoplasms, Mutation, Prognosis, Genes, ras, Likelihood Functions, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, 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

Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks