KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer

Lièvre, Astrid; Bachet, Jean-Baptiste; Le Corre, Delphine; Boige, Valérie; Landi, Bruno; Emile, Jean-François; Côté, Jean-François; Tomasic, Gorana; Penna, Christophe; Ducreux, Michel; Rougier, Philippe; Penault-Llorca, Frédérique; Laurent-Puig, Pierre

doi:10.1158/0008-5472.can-06-0191

Cited by 2,229Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsGenetic factors in colorectal cancer

KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer

Lièvre, Astrid, Bachet, Jean-Baptiste, Le Corre, Delphine, Boige, Valérie, Landi, Bruno, Emile, Jean-François, Côté, Jean-François, Tomasic, Gorana +5 more·2006·Cancer Research

DOI 10.1158/0008-5472.can-06-0191

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Abstract

The anti-epidermal growth factor receptor (anti-EGFR) cetuximab has been proven to be efficient in metastatic colorectal cancer. The molecular mechanisms underlying the clinical response to this drug remain unknown. Genetic alterations of the intracellular effectors involved in EGFR-related signaling pathways may have an effect on response to this targeted therapy. In this study, tumors from 30 metastatic colorectal cancer patients treated by cetuximab were screened for KRAS, BRAF, and PIK3CA mutation by direct sequencing and for EGFR copy number by chromogenic in situ hybridization. Eleven of the 30 patients (37%) responded to cetuximab. A KRAS mutation was found in 13 tumors (43%) and was significantly associated with the absence of response to cetuximab (KRAS mutation in 0% of the 11 responder patients versus 68.4% of the 19 nonresponder patients; P = 0.0003). The overall survival of patients without KRAS mutation in their tumor was significantly higher compared with those patients with a mutated tumor (P = 0.016; median, 16.3 versus 6.9 months). An increased EGFR copy number was found in 3 patients (10%) and was significantly associated with an objective tumor response to cetuximab (P = 0.04). In conclusion, in this study, KRAS mutations are a predictor of resistance to cetuximab therapy and are associated with a worse prognosis. The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment. (Cancer Res 2006; 66(8): 3992-5)

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Cetuximab has a notable lack of activity in KRAS-mutant CRC patients.
“in line with its notable lack of activity in KRAS -mutant CRC patients [18].”
From Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor (2022) · cites this paper as [18]
KRAS exon 2 mutations are major determinants of primary resistance to cetuximab or panitumumab.
“as major determinants of primary resistance to cetuximab or panitumumab [17, 27-29].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [17]
In patients who progressed after chemotherapy, all 11 responders to cetuximab-irinotecan were KRAS wild-type, while 13 of 19 non-responders had KRAS mutations.
“Lievre et al. assessed the effectiveness of a cetuximab–irinotecan combination in patients who had progressed following chemotherapy, revealing that all 11 patients responding to treatment were KRAS WT, while 13 out of 19 non-responders had KRAS mutations [11].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [11]

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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 · see citing works
High Frequency of Mutations of the PIK3CA Gene in Human Cancers
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448 · see citing works
Phase II Trial of Cetuximab in Patients With Refractory Colorectal Cancer That Expresses the Epidermal Growth Factor Receptor
Saltz, L. B., Meropol, N. J., Loehrer, P. J., Needle, M. N., Kopit, J., & Mayer, R. J. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.10.182 · Cited by 1,694 · 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
Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry.
Chung, K. Y., Shia, J., Kemeny, N. E., Shah, M., Schwartz, G. K., Tse, A., Hamilton, A., Pan, D., Schrag, D., Schwartz, L., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.08.037 · Cited by 1,081 · 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
Kirsten ras mutations in patients with colorectal cancer: The multicenter “RASCAL” study
Andreyev, H. J. N., Norman, A. R., Clarke, P. A., Cunningham, D., & Oates, J. R. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.9.675 · Cited by 748 · see citing works
The Price Tag on Progress — Chemotherapy for Colorectal Cancer
Schrag, D. (2004) · New England Journal of Medicine · doi:10.1056/nejmp048143 · Cited by 437 · see citing works
Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study
Shia, J., Klimstra, D. S., Li, A. R., Qin, J., Saltz, L. B., Teruya‐Feldstein, J., Akram, M. M., Chung, K. Y., Yao, D. X., Paty, P. B., et al. (2005) · Modern Pathology · doi:10.1038/modpathol.3800417 · Cited by 163 · see citing works
Molecular Alterations in Tumors and Response to Combination Chemotherapy with Gefitinib for Advanced Colorectal Cancer
Ogino, S., Meyerhardt, J. A., Cantor, M., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0738 · Cited by 156 · see citing works
Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti‐EGFR therapy?
Sauer, T., Guren, M. G., Norèn, T., et al. (2005) · Histopathology · doi:10.1111/j.1365-2559.2005.02252.x · Cited by 46 · see citing works

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Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3599 · Cited by 4,681 · see citing works
Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer
Van Cutsem, E., Köhne, C.-H., Hitre, E., Zaluski, J., Chang Chien, C.-R., Makhson, A., D'Haens, G., Pintér, T., Lim, R., Bodoky, G., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805019 · Cited by 3,877 · see citing works
Self-citation
K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622 · 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
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557 · see citing works
Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer
Japanese Society for Cancer of the Colon and Rectum, Watanabe, T., Muro, K., Ajioka, Y., Hashiguchi, Y., Ito, Y., Saito, Y., Hamaguchi, T., Ishida, H., Ishiguro, M., et al. (2018) · International Journal of Clinical Oncology · doi:10.1007/s10147-017-1101-6 · Cited by 2,467 · see citing works
“• The usefulness of anti-EGFR antibody drugs has been reported in metastatic colorectal cancer without KRAS gene mutations [38–41, 47, 53, 55, 85–90].”
Background
Open-Label Phase III Trial of Panitumumab plus Best Supportive Care Compared with Best Supportive Care Alone in Patients with Chemotherapy-Refractory Metastatic Colorectal Cancer
Van Cutsem, E., Peeters, M., Siena, S., Humblet, Y., Hendlisz, A., Neyns, B., Canon, J.-L., Van Laethem, J.-L., Maurel, J., Richardson, G., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.1620 · Cited by 1,979 · see citing works
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
Hong, D. S., Fakih, M. G., Strickler, J. H., Desai, J., Durm, G. A., Shapiro, G. I., Falchook, G. S., Price, T. J., Sacher, A., Denlinger, C. S., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1917239 · Cited by 1,733 · see citing works
Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
Di Nicolantonio, F., Martini, M., Molinari, F., Sartore-Bianchi, A., Arena, S., Saletti, P., De Dosso, S., Mazzucchelli, L., Frattini, M., Siena, S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0786 · Cited by 1,591 · see citing works
Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers
Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330 · see citing works
Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial
Maughan, T. S., Adams, R. A., Smith, C. G., Meade, A. M., Seymour, M. T., Wilson, R. H., Idziaszczyk, S., Harris, R., Fisher, D., Kenny, S. L., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60613-2 · Cited by 960 · see citing works
Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH
Yun, J., Mullarky, E., Lu, C., Bosch, K. N., Kavalier, A., Rivera, K., Roper, J., Chio, I. I. C., Giannopoulou, E. G., Rago, C., et al. (2015) · Science · doi:10.1126/science.aaa5004 · Cited by 913 · see citing works
Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies
Lipson, D., Capelletti, M., Yelensky, R., Otto, G., Parker, A., Jarosz, M., Curran, J. A., Balasubramanian, S., Bloom, T., Brennan, K. W., et al. (2012) · Nature Medicine · doi:10.1038/nm.2673 · Cited by 869 · 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
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
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, 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 · 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
Understanding resistance to EGFR inhibitors—impact on future treatment strategies
Wheeler, D. L., Dunn, E. F., & Harari, P. M. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.97 · Cited by 683 · 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
Self-citation
A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets
Deng, N., Goh, L. K., Wang, H., Das, K., Tao, J., Tan, I. B., Zhang, S., Lee, M., Wu, J., Lim, K. H., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-301839 · Cited by 645 · see citing works
Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy
Becht, E., de Reyniès, A., Giraldo, N. A., Pilati, C., Buttard, B., Lacroix, L., Selves, J., Sautès-Fridman, C., Laurent-Puig, P., & Fridman, W. H. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2879 · Cited by 590 · see citing works
Self-citation
Pathways of Colorectal Carcinogenesis
Nguyen, L. H., Goel, A., & Chung, D. C. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.08.059 · Cited by 606 · see citing works
Final Results from PRIME: Randomized Phase III Study of Panitumumab with FOLFOX4 for First-Line Treatment of Metastatic Colorectal Cancer
Douillard, J. Y., Siena, S., Cassidy, J., Tabernero, J., Burkes, R., Barugel, M., Humblet, Y., Bodoky, G., Cunningham, D., Jassem, J., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu141 · Cited by 606 · see citing works
EGFR 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
KRAS and BRAF Mutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial
Richman, S. D., Seymour, M. T., Chambers, P., Elliott, F., Daly, C. L., Meade, A. M., Taylor, G., Barrett, J. H., & Quirke, P. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.4295 · Cited by 560 · see citing works
KRAS Mutations in Non-Small Cell Lung Cancer
Riely, G. J., Marks, J., & Pao, W. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200809-107lc · Cited by 550 · see citing works
Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor
Hallin, J., Bowcut, V., Calinisan, A., Briere, D. M., Hargis, L., Engstrom, L. D., Laguer, J., Medwid, J., Vanderpool, D., Lifset, E., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02007-7 · Cited by 533 · 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
A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma
Hamid, O., Schmidt, H., Nissan, A., Ridolfi, L., Aamdal, S., Hansson, J., Guida, M., Hyams, D. M., Gómez, H., Bastholt, L., et al. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-204 · Cited by 534 · 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
Resistance to anti-EGFR therapy in colorectal cancer: From heterogeneity to convergent evolution
Misale, S., Di Nicolantonio, F., Sartore-Bianchi, A., Siena, S., & Bardelli, A. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0462 · Cited by 513 · see citing works
Impact of FcγRIIa-FcγRIIIa Polymorphisms and KRAS Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan
Bibeau, F., Lopez-Crapez, E., Di Fiore, F., Thezenas, S., Ychou, M., Blanchard, F., Lamy, A., Penault-Llorca, F., Frébourg, T., Michel, P., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0463 · Cited by 521 · see citing works
Self-citation
PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab.
Jhawer, M., Goel, S., Wilson, A. J., Montagna, C., Ling, Y.-H., Byun, D.-S., Nasser, S., Arango, D., Shin, J., Klampfer, L., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5659 · Cited by 460 · 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
Prevalence and Heterogeneity of KRAS, BRAF, and PIK3CA Mutations in Primary Colorectal Adenocarcinomas and Their Corresponding Metastases
Baldus, S. E., Schaefer, K.-L., Engers, R., Hartleb, D., Stoecklein, N. H., & Gabbert, H. E. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2446 · Cited by 432 · see citing works
PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients
Perrone, F., Lampis, A., Orsenigo, M., Di Bartolomeo, M., Gevorgyan, A., Losa, M., Frattini, M., Riva, C., Andreola, S., Bajetta, E., et al. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn541 · Cited by 410 · see citing works
Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer
Vaughn, C. P., ZoBell, S. D., Furtado, L. V., Baker, C. L., & Samowitz, W. S. (2011) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20854 · Cited by 377 · see citing works
Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer.
Neumann, J., Zeindl-Eberhart, E., Kirchner, T., & Jung, A. (2009) · Pathology - Research and Practice · doi:10.1016/j.prp.2009.07.010 · Cited by 361 · see citing works
Overcoming resistance to tumor-targeted and immune-targeted therapies
Aldea, M., Andre, F., Marabelle, A., Dogan, S., Barlesi, F., & Soria, J.-C. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1638 · Cited by 311 · see citing works
Translational value of mouse models in oncology drug development
Gould, S. E., Junttila, M. R., & de Sauvage, F. J. (2015) · Nature Medicine · doi:10.1038/nm.3853 · Cited by 293 · see citing works
PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer
Prenen, H., De Schutter, J., Jacobs, B., De Roock, W., Biesmans, B., Claes, B., Lambrechts, D., Van Cutsem, E., & Tejpar, S. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2961 · Cited by 291 · see citing works
Genomic and Biological Characterization of Exon 4 KRAS Mutations in Human Cancer
Janakiraman, M., Vakiani, E., Zeng, Z., Pratilas, C. A., Taylor, B. S., Chitale, D., Halilovic, E., Wilson, M., Huberman, K., Ricarte Filho, J. C., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0192 · Cited by 290 · see citing works
EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients
Cappuzzo, F., Finocchiaro, G., Rossi, E., Jänne, P. A., Carnaghi, C., Calandri, C., Bencardino, K., Ligorio, C., Ciardiello, F., Pressiani, T., et al. (2008) · Annals of Oncology · doi:10.1093/annonc/mdm492 · Cited by 267 · see citing works
Transcriptional Pathway Signatures Predict MEK Addiction and Response to Selumetinib (AZD6244)
Dry, J. R., Pavey, S., Pratilas, C. A., Harbron, C., Runswick, S., Hodgson, D., Chresta, C., McCormack, R., Byrne, N., Cockerill, M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1577 · Cited by 262 · 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
Prognostic and Predictive Roles of KRAS Mutation in Colorectal Cancer
Arrington, A. K., Heinrich, E. L., Lee, W., Duldulao, M., Patel, S., Sanchez, J., Garcia-Aguilar, J., & Kim, J. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131012153 · Cited by 244 · see citing works
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Hurwitz, H. I., Yi, J., Ince, W., Novotny, W. F., & Rosen, O. (2009) · The Oncologist · doi:10.1634/theoncologist.2008-0213 · Cited by 239 · see citing works
High Concordance of KRAS Status Between Primary Colorectal Tumors and Related Metastatic Sites: Implications for Clinical Practice
Santini, D., Loupakis, F., Vincenzi, B., Floriani, I., Stasi, I., Canestrari, E., Rulli, E., Maltese, P. E., Andreoni, F., Masi, G., et al. (2008) · The Oncologist · doi:10.1634/theoncologist.2008-0181 · Cited by 234 · see citing works
Recurrent KRAS codon 146 mutations in human colorectal cancer
Edkins, S., & O’Meara, S. (2006) · Cancer Biology & Therapy · doi:10.4161/cbt.5.8.3251 · Cited by 229 · see citing works
Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives
Martinelli, E., Ciardiello, D., Martini, G., Troiani, T., Cardone, C., Vitiello, P. P., Normanno, N., Rachiglio, A. M., Maiello, E., Latiano, T., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2019.10.007 · Cited by 225 · see citing works
KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer
Tie, J., Lipton, L., Desai, J., Gibbs, P., Jorissen, R. N., Christie, M., Drummond, K. J., Thomson, B. N. J., Usatoff, V., Evans, P. M., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1720 · Cited by 217 · see citing works
Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers
Ebi, H., Corcoran, R. B., Singh, A., Chen, Z., Song, Y., Lifshits, E., Ryan, D. P., Meyerhardt, J. A., Benes, C., Settleman, J., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57909 · Cited by 210 · see citing works
KRAS G12D Mutation Subtype Is A Prognostic Factor for Advanced Pancreatic Adenocarcinoma
Bournet, B., Muscari, F., Buscail, C., Assenat, E., Barthet, M., Hammel, P., Selves, J., Guimbaud, R., Cordelier, P., & Buscail, L. (2016) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2016.18 · Cited by 205 · see citing works
PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis.
Mao, C., Yang, Z. Y., Hu, X. F., Chen, Q., & Tang, J. L. (2012) · Annals of Oncology · doi:10.1093/annonc/mdr464 · Cited by 188 · see citing works
Practical and robust identification of molecular subtypes in colorectal cancer by immunohistochemistry
Trinh, A., Trumpi, K., De Sousa E Melo, F., Wang, X., de Jong, J. H., Fessler, E., Kuppen, P. J. K., Reimers, M. S., Swets, M., Koopman, M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0680 · Cited by 180 · see citing works
Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients
Cappuzzo, F., Varella-Garcia, M., Finocchiaro, G., Skokan, M., Gajapathy, S., Carnaghi, C., Rimassa, L., Rossi, E., Ligorio, C., Di Tommaso, L., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604439 · Cited by 178 · see citing works
KRAS mutation correlates with accelerated metastatic progression in patients with colorectal liver metastases
Nash, G. M., Gimbel, M., Shia, J., Nathanson, D. R., Ndubuisi, M. I., Zeng, Z.-S., Kemeny, N., & Paty, P. B. (2010) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0605-3 · Cited by 172 · see citing works
Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer
Ishaque, N., Abba, M. L., Hauser, C., Patil, N., Paramasivam, N., Huebschmann, D., Leupold, J. H., Balasubramanian, G. P., Kleinheinz, K., Toprak, U. H., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07041-z · Cited by 132 · see citing works
Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab
Dunn, E. F., Iida, M., Myers, R. A., Campbell, D. A., Hintz, K. A., Armstrong, E. A., Li, C., & Wheeler, D. L. (2011) · Oncogene · doi:10.1038/onc.2010.430 · Cited by 133 · see citing works
“Furthermore, it has been demonstrated in several clinical trials that patients with mCRC and a KRAS mutation do not respond to cetuximab therapy (Lievre et al., 2006; Benvenuti et al., 2007; Di Fiore et al., 2007; Khambata-Ford et al., 2007; Cappuzzo et al., 2008; De Roock et al., 2008; Karapetis et al., 2008).”
Background
A combined oncogenic pathway signature of BRAF , KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction
Tian, S., Simon, I., Moreno, V., Roepman, P., Tabernero, J., Snel, M., van't Veer, L., Salazar, R., Bernards, R., & Capella, G. (2013) · Gut · doi:10.1136/gutjnl-2012-302423 · Cited by 128 · see citing works
Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer
Sforza, V., Martinelli, E., Ciardiello, F., Gambardella, V., Napolitano, S., Martini, G., della Corte, C., Cardone, C., Ferrara, M. L., Reginelli, A., et al. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i28.6345 · Cited by 123 · see citing works
Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant
Molinari, F., Martin, V, Saletti, P., De Dosso, S., Spitale, A., Camponovo, A., Bordoni, A., Crippa, S., Mazzucchelli, L., & Frattini, M. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604848 · Cited by 122 · 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
Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization
Cho, J., Chen, L., Sangji, N., Okabe, T., Yonesaka, K., Francis, J. M., Flavin, R. J., Johnson, W., Kwon, J., Yu, S., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1145 · Cited by 117 · see citing works
KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: Biological and clinical implications
Italiano, A., Hostein, I., Soubeyran, I., Fabas, T., Benchimol, D., Evrard, S., Gugenheim, J., Becouarn, Y., Brunet, R., Fonck, M., et al. (2010) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0864-z · Cited by 114 · see citing works
Oncogenic mutations as predictive factors in colorectal cancer
Lièvre, A., Blons, H., & Laurent-Puig, P. (2010) · Oncogene · doi:10.1038/onc.2010.89 · Cited by 117 · see citing works
Self-citation
Lack of Correlation between Epidermal Growth Factor Receptor Status and Response to Panitumumab Monotherapy in Metastatic Colorectal Cancer
Hecht, J. R., Mitchell, E., Neubauer, M. A., Burris, H. A., Swanson, P., Lopez, T., Buchanan, G., Reiner, M., Gansert, J., & Berlin, J. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2017 · Cited by 110 · see citing works
Association between KRAS mutation and lung metastasis in advanced colorectal cancer
Pereira, A. A. L., Rego, J. F. M., Morris, V, Overman, M. J., Eng, C., Garrett, C. R., Boutin, A. T., Ferrarotto, R., Lee, M., Jiang, Z.-Q., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2014.619 · Cited by 94 · see citing works
MEK1/2 Inhibitors AS703026 and AZD6244 May Be Potential Therapies for KRAS Mutated Colorectal Cancer That Is Resistant to EGFR Monoclonal Antibody Therapy
Yoon, J., Koo, K.-H., & Choi, K.-Y. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3058 · Cited by 92 · see citing works
Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies
Leto, S. M., & Trusolino, L. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1161-2 · Cited by 87 · see citing works
Heterogeneity of KRAS status may explain the subset of discordant KRAS status between primary and metastatic colorectal cancer
Watanabe, T., Kobunai, T., Yamamoto, Y., Matsuda, K., Ishihara, S., Nozawa, K., Iinuma, H., Shibuya, H., & Eshima, K. (2011) · Diseases of the Colon & Rectum · doi:10.1097/dcr.0b013e31821d37a3 · Cited by 82 · see citing works
Efficacy of the Monoclonal Antibody EGFR Inhibitors for the Treatment of Metastatic Colorectal Cancer
Fakih, M., & Wong, R. (2010) · Current Oncology · doi:10.3747/co.v17is1.616 · Cited by 76 · see citing works
Concomitant mutations and splice variants in KRAS and BRAF demonstrate complex perturbation of the Ras/Raf signalling pathway in advanced colorectal cancer
Seth, R., Crook, S., Ibrahem, S., Fadhil, W., Jackson, D., & Ilyas, M. (2009) · Gut · doi:10.1136/gut.2008.159137 · Cited by 66 · see citing works
Comprehensive Clinical and Molecular Characterization of KRASG12C-Mutant Colorectal Cancer
Henry, J. T., Coker, O., Chowdhury, S., Shen, J. P., Morris, V. K., Dasari, A., Raghav, K., Nusrat, M., Kee, B., Parseghian, C., et al. (2021) · JCO Precision Oncology · doi:10.1200/po.20.00256 · Cited by 66 · see citing works
KRAS Mutation Status Is Associated with Enhanced Dependency on Folate Metabolism Pathways in Non–Small Cell Lung Cancer Cells
Moran, D. M., Trusk, P. B., Pry, K., Paz, K., Sidransky, D., & Bacus, S. S. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0649 · Cited by 64 · see citing works
Repurposing of Cetuximab in antibody-directed chemotherapy-loaded nanoparticles in EGFR therapy-resistant pancreatic tumours
McDaid, W. J., Greene, M. K., Johnston, M. C., Pollheimer, E., Smyth, P., McLaughlin, K., Van Schaeybroeck, S., Straubinger, R. M., Longley, D. B., & Scott, C. J. (2019) · Nanoscale · doi:10.1039/c9nr07257h · Cited by 58 · see citing works
Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers
Serebriiskii, I. G., Pavlov, V., Tricarico, R., Andrianov, G., Nicolas, E., Parker, M. I., Newberg, J., Frampton, G., Meyer, J. E., & Golemis, E. A. (2022) · Nature Communications · doi:10.1038/s41467-022-29227-2 · Cited by 55 · see citing works
Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Hao, H.-X., Wang, H., Liu, C., Kovats, S., Velazquez, R., Lu, H., Pant, B., Shirley, M., Meyer, M. J., Pu, M., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0170 · Cited by 53 · see citing works
IL-15 and IL-2 increase cetuximab-mediated cellular cytotoxicity against triple negative breast cancer cell lines expressing EGFR
Roberti, M. P., Barrio, M. M., Bravo, A. I., Rocca, Y. S., Arriaga, J. M., Bianchini, M., Mordoh, J., & Levy, E. M. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1360-2 · Cited by 51 · see citing works
L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells
Jung, S.-A., Lee, D.-H., Moon, J.-H., Hong, S.-W., Shin, J.-S., Hwang, I. Y., Shin, Y. J., Kim, J. H., Gong, E.-Y., Kim, S.-M., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.009 · Cited by 47 · see citing works
Methylglyoxal Scavengers Resensitize KRAS-Mutated Colorectal Tumors to Cetuximab
Bellier, J., Nokin, M.-J., Caprasse, M., Tiamiou, A., Blomme, A., Scheijen, J. L., Koopmansch, B., MacKay, G. M., Chiavarina, B., Costanza, B., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.012 · Cited by 38 · see citing works
Restoring PUMA induction overcomes KRAS-mediated resistance to anti-EGFR antibodies in colorectal cancer
Knickelbein, K., Tong, J., Chen, D., Wang, Y.-J., Misale, S., Bardelli, A., Yu, J., & Zhang, L. (2018) · Oncogene · doi:10.1038/s41388-018-0289-x · Cited by 33 · see citing works
Causal Evidence and Dispositions in Medicine and Public Health
Rocca, E., & Anjum, R. L. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17061813 · Cited by 27 · see citing works
The Prognostic Role of Ephrin A2 and Endothelial Growth Factor Receptor Pathway Mediators in Patients With Advanced Colorectal Cancer Treated With Cetuximab
Strimpakos, A., Pentheroudakis, G., Kotoula, V., De Roock, W., Kouvatseas, G., Papakostas, P., Makatsoris, T., Papamichael, D., Andreadou, A., Sgouros, J., et al. (2013) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2013.07.001 · Cited by 27 · see citing works
Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer
Augustine, T. A., Baig, M., Sood, A., Budagov, T., Atzmon, G., Mariadason, J. M., Aparo, S., Maitra, R., & Goel, S. (2015) · British Journal of Cancer · doi:10.1038/bjc.2014.561 · Cited by 27 · see citing works
Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer
Omolo, B., Yang, M., Lo, F. Y., Schell, M. J., Austin, S., Howard, K., Madan, A., & Yeatman, T. J. (2016) · BMC Medical Genomics · doi:10.1186/s12920-016-0225-2 · Cited by 25 · see citing works
Maintenance Treatment with Cetuximab and BAY86-9766 Increases Antitumor Efficacy of Irinotecan plus Cetuximab in Human Colorectal Cancer Xenograft Models
Troiani, T., Napolitano, S., Martini, G., Martinelli, E., Cardone, C., Normanno, N., Vitagliano, D., Morgillo, F., Fenizia, F., Lambiase, M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0211 · Cited by 18 · see citing works
Impact of KRASG12 mutations on survival with trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer: Post hoc analysis of the phase III SUNLIGHT trial
Tabernero, J., Taieb, J., Fakih, M., Prager, G. W., Van Cutsem, E., Ciardiello, F., Mayer, R. J., Amellal, N., Skanji, D., Calleja, E., et al. (2024) · ESMO Open · doi:10.1016/j.esmoop.2024.102945 · Cited by 18 · see citing works
RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches
Sütcüoğlu, O., Yıldırım, H. Ç., Almuradova, E., Günenç, D., & Yalçın, Ş. (2025) · Medicina · doi:10.3390/medicina61071202 · Cited by 10 · see citing works
Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges
Al-Hujaily, E. M., Al-Sowayan, B. S., Alyousef, Z., Uddin, S., & Alammari, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213696 · Cited by 6 · see citing works

The Cost Study of Cetuximab and Panitumumab in The First-Line Treatment of Mcrc in The Czech Republic
Hradecká, I., Říhová, B., & Demlová, R. (2017) · Value in Health · doi:10.1016/j.jval.2017.08.162
Treatment with Panitumumab After a Severe Infusion Reaction to Cetuximab in a Patient with Metastatic Colorectal Cancer: A Case Report
Heun, J. M., & Holen, K. D. (2007) · Clinical Colorectal Cancer · doi:10.3816/ccc.2007.n.019 · Cited by 45 · see citing works
The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience
Gürsoy, P., Çakar, B., Almuradova, E., et al. (2020) · Journal of Chemotherapy · doi:10.1080/1120009x.2020.1861531 · Cited by 2 · see citing works
Targeting colorectal cancer with human anti-EGFR monoclonocal antibodies: focus on panitumumab
Grothey, A. F. (2008) · Biologics · doi:10.2147/btt.s1980 · Cited by 49 · see citing works
ASPECCT: panitumumab versus cetuximab for colorectal cancer
Goss, P. E., Bl, L.-B., Wang, J., et al. (2014)

Authors: Lièvre, A., Bachet, J.-B., Le Corre, D., Boige, V., Landi, B., Emile, J.-F., Côté, J.-F., Tomasic, G., Penna, C., Ducreux, M., Rougier, P., Penault-Llorca, F., & Laurent-Puig, P.
Affiliations: 1Université Paris-Descartes, Institut National de la Sante et de la Recherche Medicale UMR-775;
Université de Versailles Saint-Quentin-en-Yvelines (FR)
4Institut Gustave Roussy, Villejuif, France; and
Hôpital Européen Georges-Pompidou (FR)
3Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise Paré, Boulogne Billancourt, France, Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France;
Inserm (FR)
Institut Gustave Roussy (FR)
5Centre Jean Perrin, Clermont-Ferrand, France, Université Auvergne, Clermont-Ferrand, France
ORCID: Bachet, Jean-Baptiste
Ducreux, Michel
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2006-04-15
Volume: 66
Issue: 8
Pages: 3992-3995
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-06-0191
OpenAlex: W2164837623
Cited by: 2,229
References: 11
Citations by year: 2026: 18 · 2025: 45 · 2024: 45 · 2023: 52 · 2022: 100 · 2021: 92 · 2020: 90 · 2019: 102 · 2018: 95 · 2017: 106 · 2016: 137 · 2015: 152 · 2014: 145 · 2013: 145 · 2012: 157
FWCI: 70.39
Type: journal article
Language: en
Open access: closed
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: KRAS mutation, cetuximab, metastatic colorectal cancer, EGFR, predictive biomarkers, treatment response, BRAF mutation, PIK3CA mutation, overall survival, drug resistance
MeSH terms: Cetuximab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Female, Gene Amplification, Humans, Male, Middle Aged, Mutation, Predictive Value of Tests, Genes, ras, Colorectal Neoplasms, Gene Dosage, Genes, erbB-1, Antibodies, Monoclonal, Humanized, ErbB Receptors

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KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer

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