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Increased Detection Sensitivity for KRAS Mutations Enhances the Prediction of Anti-EGFR Monoclonal Antibody Resistance in Metastatic Colorectal Cancer
Abstract
Purpose: KRAS mutations represent the main cause of resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) in metastatic colorectal cancer (mCRC). We evaluated whether highly sensitive methods for KRAS investigation improve the accuracy of predictions of anti-EGFR MoAbs efficacy. Experimental Design: We retrospectively evaluated objective tumor responses in mCRC patients treated with cetuximab or panitumumab. KRAS codons 12 and 13 were examined by direct sequencing, MALDI-TOF MS, mutant-enriched PCR, and engineered mutant-enriched PCR, which have a sensitivity of 20%, 10%, 0.1%, and 0.1%, respectively. In addition, we analyzed KRAS codon 61, BRAF, and PIK3CA by direct sequencing and PTEN expression by immunohistochemistry. Results: In total, 111 patients were considered. Direct sequencing revealed mutations in codons 12 and 13 of KRAS in 43/111 patients (39%) and BRAF mutations in 9/111 (8%), with almost all of these occurring in nonresponder patients. Using highly sensitive methods, we identified up to 13 additional KRAS mutations compared with direct sequencing, all occurring in nonresponders. By analyzing PIK3CA and PTEN, we found that of these 13 patients, 7 did not show any additional alteration in the PI3K pathway. Conclusions: The application of highly sensitive methods for the detection of KRAS mutations significantly improves the identification of mCRC patients resistant to anti-EGFR MoAbs. Clin Cancer Res; 17(14); 4901–14. ©2011 AACR.
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“Non V600E mutations, other than Q524L, may also contribute to primary resistance to anti-EGFR mAbs [25, 96].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [96]
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“The prevalence of BRAF V600E mutations in mCRC is 8–10%, and they occur mutually exclusively with KRAS mutations [25, 96].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [96]
Citations
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660
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
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
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
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
De Roock, W., Claes, B., Bernasconi, D., De Schutter, J., Biesmans, B., Fountzilas, G., Kalogeras, K. T., Kotoula, V., Papamichael, D., Laurent-Puig, P., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70130-3 · Cited by 2,144
Self-citationEGFR Antagonists in Cancer Treatment
Ciardiello, F., & Tortora, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707704 · Cited by 2,095
Douillard, J., Siena, S., Cassidy, J., Tabernero, J. M., Burkes, R. L., Barugel, M. E., Humblet, Y., Bodoky, G., Cunningham, D., Jassem, J., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4860 · Cited by 1,829
Bokemeyer, C., Bondarenko, I., Makhson, A. M., Hartmann, J. T., Aparicio, J., de Braud, F., Donea, S., Ludwig, H., Schuch, G., Stroh, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.8397 · Cited by 1,646
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 · cited 5×
“Furthermore, mutational analyses were performed using widely accepted protocols (4, 17), and the laboratory”
BackgroundMethodResultInfluentialSelf-citationLièvre, 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 1,485
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 · cited 1×
“All KRAS mutated cases were BRAF wild type and vice-versa, confirming data from the literature (32).”
BackgroundSelf-citationAllegra, C. J., Jessup, J. M., Somerfield, M. R., Hamilton, S. R., Hammond, E. H., Hayes, D. F., McAllister, P. K., Morton, R. F., & Schilsky, R. L. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.21.9170 · Cited by 1,156
High-throughput oncogene mutation profiling in human cancer
Thomas, R. K., Baker, A. C., Debiasi, R. M., Winckler, W., LaFramboise, T., Lin, W. M., Wang, M., Feng, W., Zander, T., MacConaill, L. E., et al. (2007) · Nature Genetics · doi:10.1038/ng1975 · Cited by 978
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
Self-citationDe 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
De Roock, W., Jonker, D. J., Di Nicolantonio, F., Sartore-Bianchi, A., Tu, D., Siena, S., Lamba, S., Arena, S., Frattini, M., Piessevaux, H., et al. (2010) · JAMA · doi:10.1001/jama.2010.1535 · Cited by 748
Self-citationKirsten 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
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
Self-citationSartore-Bianchi, A., Martini, M., Molinari, F., Veronese, S., Nichelatti, M., Artale, S., Di Nicolantonio, F., Saletti, P., De Dosso, S., Mazzucchelli, L., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2466 · Cited by 739
Self-citationLinardou, 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
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
Loupakis, F., Ruzzo, A., Cremolini, C., Vincenzi, B., Salvatore, L., Santini, D., Masi, G., Stasi, I., Canestrari, E., Rulli, E., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605177 · Cited by 574
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 · cited 4×
“Furthermore, mutational analyses were performed using widely accepted protocols (4, 17), and the laboratory”
BackgroundMethodInfluentialSelf-citationJhawer, 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
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
Self-citationBianchi, A. S., Moroni, M., Veronese, S. M., Carnaghi, C., Bajetta, E., Luppi, G., Sobrero, A. F., Barone, C. A., Cascinu, S., Colucci, G., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.5956 · Cited by 336
van Krieken, J. H., Jung, A., Kirchner, T., Carneiro, F., Seruca, R., Bosman, F. T., Quirke, P., Fléjou, J., Hansen, T. P., Hertogh, G. D., et al. (2008) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-008-0665-y · Cited by 294
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
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
Self-citationDifferent Genetic Features Associated with Colon and Rectal Carcinogenesis
Frattini, M., Balestra, D., Suardi, S., Oggionni, M., Alberici, P., Radice, P., Costa, A., Daidone, M. G., Leo, E., Pilotti, S., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0031 · Cited by 234
Self-citationJimeno, A., Messersmith, W. A., Hirsch, F. R., Franklin, W. A., & Eckhardt, S. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.8168 · Cited by 217
Nagasaka, T., Sasamoto, H., Notohara, K., Cullings, H. M., Takeda, M., Kimura, K., Kambara, T., MacPhee, D. G., Young, J. P., Leggett, B., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.154 · Cited by 215
Nollau, P., & Wagener, C. (1997) · PubMed · Cited by 177
Evolution of intratumoral genetic heterogeneity during colorectal cancer progression
Losi, L., Baïsse, B., Bouzourène, H., & Benhattar, J. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi044 · Cited by 173
Bearzatto, A., Conte, D., Frattini, M., Zaffaroni, N., Andriani, F., Balestra, D., Tavecchio, L., Daidone, M. G., & Sozzi, G. (2002) · PubMed · Cited by 144
Self-citationMethods for detection of point mutations: performance and quality assessment
Nollau, P., Wagener, C., & Division, O. B. O. T. I. S. (1997) · Clinical Chemistry · doi:10.1093/clinchem/43.7.1114 · Cited by 143
Frattini, M., Gallino, G., Signoroni, S., Balestra, D., Lusa, L., Battaglia, L., Sozzi, G., Bertario, L., Leo, E., Pilotti, S., et al. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.021 · Cited by 136
Self-citationFranklin, W. A., Haney, J., Sugita, M., Bemis, L., Jimeno, A., & Messersmith, W. A. (2009) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2010.080131 · Cited by 111
Marchetti, A., Milella, M., Felicioni, L., Cappuzzo, F., Irtelli, L., Grammastro, M. D., Sciarrotta, M., Malatesta, S., Nuzzo, C. M. A., Finocchiaro, G., et al. (2009) · Neoplasia · doi:10.1593/neo.09814 · Cited by 98
Self-citationAlbanese, I., Scibetta, A. G., Migliavacca, M., Russo, A., Bazan, V., Tomasino, R. M., Colomba, P., Tagliavia, M., & La Farina, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.10.111 · Cited by 91
Schimanski, C. C., Linnemann, U., & Berger, M. R. (1999) · PubMed · Cited by 72
A comparability study of 5 commercial KRAS tests
Oliner, K. S., Juan, T., Suggs, S., Wolf, M., Sarosi, I., Freeman, D. J., Gyuris, T., Baron, W., Bakker, A., Parker, A. N., et al. (2010) · Diagnostic Pathology · doi:10.1186/1746-1596-5-23 · Cited by 52
Martin, V., Mazzucchelli, L., & Frattini, M. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2008.059592 · Cited by 46
Self-citationHaug, U., Hillebrand, T., Bendzkô, P., Löw, M., Rothenbacher, D., Stegmaier, C., & Brenner, H. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2006.078188 · Cited by 27
K-rasMutations and Cetuximab in Colorectal Cancer
Marchetti, A., & Gasparini, G. (2009) · New England Journal of Medicine · doi:10.1056/nejmc082346 · Cited by 24
Self-citationDetection of the Mutated K-Ras Biomarker in Colorectal Carcinoma
Doolittle, B. R., Emanuel, J. R., Tuttle, C., & Costa, J. C. (2001) · Experimental and Molecular Pathology · doi:10.1006/exmp.2001.2364 · Cited by 24
Giaretti, W., Macciocu, B., Geido, E., Hermsen, M. A. J. A., Postma, C., Baak, J. P. A., Williams, R. D., & Meijer, G. A. (2000) · Analytical Cellular Pathology · doi:10.1155/2000/747524 · Cited by 23
Intratumoral Heterogeneity of Genetic Changes in Primary Colorectal Carcinomas with Metastasis
Fukunari, H., Iwama∥, T., Sugihara, K., & Miyaki, M. (2003) · Surgery Today · doi:10.1007/s10595-002-2520-1 · Cited by 22
Salbe, C., Trevisiol, C., Ferruzzi, E., Mancuso, T., Nascimbeni, R., Fabio, F. D., Salerni, B., & Dittadi, R. (2000) · The International Journal of Biological Markers · doi:10.1177/172460080001500404 · Cited by 17
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Metadata
- Authors
- Molinari, F., Felicioni, L., Buscarino, M., De Dosso, S., Buttitta, F., Malatesta, S., Movilia, A., Luoni, M., Boldorini, R., Alabiso, O., Girlando, S., Soini, B., Spitale, A., Di Nicolantonio, F., Saletti, P., Crippa, S., Mazzucchelli, L., Marchetti, A., Bardelli, A., & Frattini, M.
- Affiliations
- Istituto Oncologico della Svizzera Italiana (CH)
- Authors' Affiliations: 1Institute of Pathology; 2Ticino Cancer Registry, Locarno, Switzerland; 3Department of Pathology, Clinical Research Center, Center of Excellence on Aging, University-Foundation, Chieti, Italy; 4Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Candiolo, Italy; 5Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Departments of 6Pathology and 7Oncology, Civil Hospital, Legnano, Italy; Departments of 8Medical Sciences and 9Oncology, University School of Medicine, Novara, Italy; Departments of 10Pathology and 11Medical Oncology, Santa Chiara Hospital, Trento, Italy; and 12FIRC Institute of Molecular Oncology, Milan, Italy
- Istituto Cantonale di Patologia (CH)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2011-07-15
- Volume
- 17
- Issue
- 14
- Pages
- 4901-4914
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2135672185
- Cited by
- 159
- References
- 51
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 8 · 2017: 11 · 2016: 14 · 2015: 20 · 2014: 27 · 2013: 26 · 2012: 26
- FWCI
- 13.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- 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, metastatic colorectal cancer, anti-EGFR monoclonal antibody, cetuximab, panitumumab, treatment resistance, BRAF mutation, PIK3CA, PTEN, PI3K signaling, MALDI-TOF mass spectrometry, direct sequencing, predictive biomarkers
- MeSH terms
- Aged, Antibodies, Monoclonal, Antineoplastic Agents, Base Sequence, Female, Humans, Male, Middle Aged, Mutation, Neoplasm Metastasis, Prognosis, Proto-Oncogene Proteins, Sensitivity and Specificity, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins p21(ras), Treatment Outcome, ras Proteins, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins B-raf, PTEN Phosphohydrolase, Kaplan-Meier Estimate, Class I Phosphatidylinositol 3-Kinases, ErbB Receptors
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