Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer

Laurent-Puig, Pierre; Cayre, Anne; Manceau, Gilles; Buc, Emmanuel; Bachet, Jean-Baptiste; Lecomte, Thierry; Rougier, Philippe; Lievre, Astrid; Landi, Bruno; Boige, Valérie; Ducreux, Michel; Ychou, Marc; Bibeau, Fréderic; Bouché, Olivier; Reid, Julia; Stone, Steven; Penault-Llorca, Frédérique

doi:10.1200/jco.2008.21.6796

Cited by 673Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsGenetic factors in colorectal cancer

Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer

Laurent-Puig, Pierre, Cayre, Anne, Manceau, Gilles, Buc, Emmanuel, Bachet, Jean-Baptiste, Lecomte, Thierry, Rougier, Philippe, Lievre, Astrid +9 more·2009·Journal of Clinical Oncology

DOI 10.1200/jco.2008.21.6796

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Abstract

Purpose: The occurrence of KRAS mutation is predictive of nonresponse and shorter survival in patients treated by anti–epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors. However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy. Patients and Methods: We retrospectively collected tumors from 173 patients with mCRC. All but one patient received a cetuximab-based regimen as second-line or greater therapy. KRAS and BRAF status were assessed by allelic discrimination. EGFR amplification was assessed by chromogenic in situ hybridization and fluorescent in situ hybridization, and the expression of PTEN was assessed by immunochemistry. Results: In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = .063) but were strongly associated with shorter progression-free survival (P < .001) and shorter overall survival (OS; P < .001). A high EGFR polysomy or an EGFR amplification was found in 17.7% of the patients and was associated with response (P = .015). PTEN null expression was found in 19.9% of the patients and was associated with shorter OS (P = .013). In multivariate analysis, BRAF mutation and PTEN expression status were associated with OS. Conclusion: BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.

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The BRAF V600E mutation is a predictor of low response rates to cetuximab and panitumumab.
“and also of low RRs to cetuximab and panitumumab [18, 20, 52, 53].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [53]
The BRAF V600E mutation is a predictor of tumor aggressiveness in metastatic colorectal cancer.
“The BRAF V600E mutation has been described as a predictor of tumor aggressiveness in metastatic disease [33, 52, 53]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [53]
Increased EGFR gene copy number could predict response among KRAS wild-type patients.
“Increased EGFR gene copy number could predict response among KRAS wild-type patients [53, 91, 111-113]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [53]
PTEN is a negative regulator in the PI3K/AKT pathway and is found in 20-40% of metastatic colorectal cancer.
“PTEN is a negative regulator in the PI3K/AKT pathway and was found in 20–40% of mCRC [106, 107].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [107]

Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674 · see citing works
Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer
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
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
Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal Cancer
Saltz, L. B., Cox, J. V., Blanke, C. D., Rosen, L. S., Fehrenbacher, L., Moore, M. J., Maroun, J. A., Ackland, S. P., Locker, P. K., Pirotta, N., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200009283431302 · Cited by 3,004 · 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
Self-citation
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
PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients
Nagata, Y., Lan, K.-H., Zhou, X., Tan, M., Esteva, F. J., Sahin, A. A., Klos, K. S., Li, P., Monia, B. P., Nguyen, N. T., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.022 · Cited by 1,858 · see citing works
A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer
Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.030 · Cited by 1,627 · 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
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
Self-citation
Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442 · see citing works
BRAF mutation predicts sensitivity to MEK inhibition
Solit, D. B., Garraway, L. A., Pratilas, C. A., Sawai, A., Getz, G. A., Basso, A., Ye, Q., Lobo, J. M., She, Y., Osman, I., et al. (2005) · Nature · doi:10.1038/nature04304 · Cited by 1,329 · 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
The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway
Sansal, I., & Sellers, W. R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.141 · Cited by 922 · 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
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
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
Multicenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines
Lenz, H., Cutsem, E. V., Khambata‐Ford, S., Mayer, R. J., Gold, P. J., Stella, P. J., Mirtsching, B. C., Cohn, A. L., Pippas, A. W., Azarnia, N., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.7595 · Cited by 522 · see citing works
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
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
BRAF Mutation Is Frequently Present in Sporadic Colorectal Cancer with Methylated hMLH1, But Not in Hereditary Nonpolyposis Colorectal Cancer
Deng, G., Bell, I., Crawley, S., Gum, J. R., Terdiman, J. P., Allen, B. A., Truta, B., Sleisenger, M. H., & Kim, Y. S. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1118-3 · Cited by 408 · see citing works
Epidermal Growth Factor Receptor Gene Copy Number and Clinical Outcome of Metastatic Colorectal Cancer Treated With Panitumumab
Bianchi, 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 332 · see citing works
Mutations in the RAS‐MAPK, PI(3)K (phosphatidylinositol‐3‐OH kinase) signaling network correlate with poor survival in a population‐based series of colon cancers
Barault, L., Veyrie, N., Jooste, V., Corre, D. L., Chapusot, C., Ferraz, J., Lièvre, A., Cortet, M., Bouvier, A., Rat, P., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23388 · Cited by 331 · see citing works
Self-citation
Association of Smoking, CpG Island Methylator Phenotype, and V600E BRAF Mutations in Colon Cancer
Samowitz, W. S., Albertsen, H., Sweeney, C., Herrick, J. S., Caan, B. J., Anderson, K. E., Wolff, R. K., & Slattery, M. L. (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj468 · Cited by 274 · see citing works
Increased EGFR Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non–Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy
Hirsch, F. R., Herbst, R. S., Olsen, C. C., Chansky, K., Crowley, J. J., Kelly, K. L., Franklin, W. A., Bunn, P. A., Varella‐Garcia, M., & Gandara, D. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.0111 · Cited by 271 · 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
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
Molecular determinants of cetuximab efficacy.
Vallböhmer, D., Zhang, W., Gordon, M., Yang, D. Y., Yun, J., Press, O. A., Rhodes, K. E., Sherrod, A. E., Iqbal, S., Danenberg, K. D., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.09.100 · Cited by 234 · 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
Clinical Usefulness of EGFR Gene Copy Number as a Predictive Marker in Colorectal Cancer Patients Treated with Cetuximab: A Fluorescent In situ Hybridization Study
Personeni, N., Fieuws, S., Piessevaux, H. H., Hertogh, G. D., Schutter, J. D., Biesmans, B., Roock, W. D., Capoen, A., Dêbiec‐Rychter, M., Laethem, J. V., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0449 · Cited by 173 · see citing works
Targeting the molecular target of rapamycin (mTOR)
Rowinsky, E. K. (2004) · Current Opinion in Oncology · doi:10.1097/01.cco.0000143964.74936.d1 · Cited by 155 · see citing works
PTEN mutations are common in sporadic microsatellite stable colorectal cancer
Nassif, N. T., Lobo, G. P., Wu, X., Henderson, C. J., Morrison, C. D., Eng, C., Jalaludin, B. B., & Segelov, E. (2004) · Oncogene · doi:10.1038/sj.onc.1207059 · Cited by 153 · see citing works
Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study
Razis, E. D., Briasoulis, E. C., Vrettou, E., Skarlos, D. V., Papamichael, D., Kostopoulos, I. S., Samantas, E., Xanthakis, I., Bobos, M., Galanidi, E., et al. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-234 · Cited by 90 · see citing works
Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number
Italiano, A., Follana, P., Caroli‐Bosc, F., Badetti, J.-L., Benchimol, D., Garnier, G., Gugenheim, J., Haudebourg, J., Keslair, F., Lesbats, G., et al. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-007-9667-2 · Cited by 86 · see citing works
Correction: Prediction of Response to Cetuximab
(2008) · Cancer Research · doi:10.1158/0008-5472.can-68-16-cor1 · Cited by 54 · see citing works
Anti-EGFR monoclonal antibodies in the treatment of non-small cell lung cancer
Bianchi, A. S., Cerea, G., Schiavetto, I., Giannetta, L. G., Ricotta, R., Maugeri, M. R., Moroni, M., Marrapese, G., & Siena, S. (2006) · Annals of Oncology · doi:10.1093/annonc/mdj922 · Cited by 4 · see citing works

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ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw235 · Cited by 3,421 · see citing works
Self-citation
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.
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 · see citing works
Self-citation
Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways
Wee, P., & Wang, Z. (2017) · Cancers · doi:10.3390/cancers9050052 · Cited by 2,027 · see citing works
Molecular Genetics of Colorectal Cancer
Fearon, E. R. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130235 · Cited by 1,805 · see citing works
Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Benson, A. B., Venook, A. P., Al-Hawary, M. M., Arain, M. A., Chen, Y., Ciombor, K. K., Cohen, S. A., Cooper, H. S., Deming, D. A., Farkas, L. M., et al. (2021) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2021.0012 · Cited by 1,709 · see citing works
Comprehensive review of targeted therapy for colorectal cancer
Xie, Y.-H., Chen, Y.-X., & Fang, J.-Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0116-z · Cited by 1,687 · see citing works
Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology
Gradishar, W. J., Anderson, B. O., Balassanian, R., Blair, S. L., Burstein, H. J., Cyr, A. E., ELIAS, A. D., Farrar, W. B., Forero, A., Giordano, S. H., et al. (2018) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2018.0012 · Cited by 1,607 · see citing works
Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours
Galon, J., Mlecnik, B., Bindea, G., Angell, H. K., Berger, A., Lagorce, C., Lugli, A., Zlobec, I., Hartmann, A., Bifulco, C. B., et al. (2013) · The Journal of Pathology · doi:10.1002/path.4287 · Cited by 1,358 · see citing works
Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology
Benson, A. B., Venook, A. P., Cederquist, L., Chan, E., Chen, Y., Cooper, H. S., Deming, D. A., Engstrom, P. F., Enzinger, P. C., Fichera, A., et al. (2017) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2017.0036 · Cited by 1,328 · see citing works
The quest to overcome resistance to EGFR-targeted therapies in cancer
Chong, C. R., & Janne, P. A. (2013) · Nature Medicine · doi:10.1038/nm.3388 · Cited by 1,055 · see citing works
Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer
Dienstmann, R., Vermeulen, L., Guinney, J., Kopetz, S., Tejpar, S., & Tabernero, J. M. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.126 · Cited by 1,038 · see citing works
Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction
Mlecnik, B., Tosolini, M., Kirilovsky, A., Berger, A., Bindea, G., Meatchi, T., Bruneval, P., Trajanoski, Z., Fridman, W.-H., Pagès, F., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.30.5425 · Cited by 1,009 · see citing works
A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer
Bertotti, A., Migliardi, G., Galimi, F., Sassi, F., Torti, D., Isella, C., Corà, D., Di Nicolantonio, F., Buscarino, M., Petti, C., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0109 · Cited by 939 · see citing works
Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer
Tran, B., Kopetz, S., Tie, J., Gibbs, P., Jiang, Z., Lieu, C. H., Agarwal, A., Maru, D. M., Sieber, O. M., & Desai, J. (2011) · Cancer · doi:10.1002/cncr.26086 · Cited by 798 · see citing works
Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study
Bokemeyer, C., Bondarenko, I., Hartmann, J. T., de Braud, F., Schuch, G., Zubel, A., Celik, I., Schlichting, M., & Koralewski, P. (2011) · Annals of Oncology · doi:10.1093/annonc/mdq632 · Cited by 775 · see citing works
Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging
Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C., Long, J. M., Laidler, P. M., Mijatović, S., Maksimović‐Ivanić, D., Stivala, F., Mazzarino, M. C., et al. (2011) · Aging · doi:10.18632/aging.100296 · Cited by 689 · see citing works
Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA
Thierry, A. R., Mouliere, F. C., Messaoudi, S. E., Mollévi, C., Lopez‐Crapez, E., Rolet, F., Gillet, B., Gongora, C., Dechelotte, P., Robert, B., et al. (2014) · Nature Medicine · doi:10.1038/nm.3511 · Cited by 681 · see citing works
Self-citation
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Nguyen, L. H., Goel, A., & Chung, D. C. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.08.059 · Cited by 606 · see citing works
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Roock, W. D., de Vriendt, V., Normanno, N., Ciardiello, F., & Tejpar, S. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70209-6 · Cited by 605 · see citing works
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Self-citation
Personalized Medicine in a Phase I Clinical Trials Program: The MD Anderson Cancer Center Initiative
Tsimberidou, A. M., Iskander, N. G., Hong, D. S., Wheler, J. J., Falchook, G. S., Fu, S., Piha-Paul, S. A., Naing, A., Jankú, F., Luthra, R., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1627 · Cited by 538 · see citing works
Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer
Siena, S., Bianchi, A. S., Nicolantonio, F. D., Balfour, J., & Bardelli, A. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djp280 · Cited by 526 · 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
Multiplex Picodroplet Digital PCR to Detect KRAS Mutations in Circulating DNA from the Plasma of Colorectal Cancer Patients
Taly, V., Pekin, D., Benhaïm, L., Kotsopoulos, S. K., Corre, D. L., Li, X., Atochin, I., Link, D. R., Griffiths, A. D., Pallier, K., et al. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2013.206359 · Cited by 494 · see citing works
Self-citation
Phase II Study of Cetuximab As First-Line Single-Drug Therapy in Patients With Unresectable Squamous Cell Carcinoma of the Skin
Maubec, E., Petrow, P. K., Scheer-Senyarich, I., Duvillard, P., Lacroix, L., Gelly, J., Certain, A., Duval, X., Crickx, B., Buffard, V., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.1735 · Cited by 469 · see citing works
BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer
Yokota, T., Ura, T., Shibata, N., Takahari, D., Shitara, K., Nomura, M., Kondo, C., Mizota, A., Utsunomiya, S., Muro, K., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.19 · Cited by 399 · see citing works
The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis
Therkildsen, C., Bergmann, T. K., Schnack, T. H., Ladelund, S., & Nilbert, M. C. (2014) · Acta Oncologica · doi:10.3109/0284186x.2014.895036 · Cited by 392 · see citing works
Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial
Seymour, M., Brown, S., Middleton, G., Maughan, T., Richman, S. D., Gwyther, S. J., Lowe, C., Seligmann, J., Wadsley, J., Maisey, N. R., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70163-3 · Cited by 387 · see citing works
Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology
Benson, A. B., Venook, A. P., Adam, M. A., Chang, G. J., Chen, Y., Ciombor, K. K., Cohen, S. A., Cooper, H. S., Deming, D. A., Garrido‐Laguna, I., et al. (2024) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2024.0029 · Cited by 406 · 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
Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer
McConkey, D. J., Choi, W., Marquis, L., Martin, F. M., Williams, M. B., Shah, J. B., Svatek, R. S., Das, A., Adam, L., Kamat, A. M., et al. (2009) · Cancer and Metastasis Reviews · doi:10.1007/s10555-009-9194-7 · Cited by 369 · see citing works
Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W. W., Cushman‐Vokoun, A. M., Funkhouser, W. K., Kopetz, S., Lieu, C. H., Lindor, N. M., Minsky, B. D., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.9807 · Cited by 365 · see citing works
Colorectal cancer molecular biology moves into clinical practice
Pritchard, C. C., & Grady, W. M. (2010) · Gut · doi:10.1136/gut.2009.206250 · Cited by 340 · see citing works
Mechanisms of resistance to anti-EGFR therapy in colorectal cancer
Zhao, B., Wang, L., Qiu, H., Zhang, M., Sun, L., Peng, P., Yu, Q., & Yuan, X. (2017) · Oncotarget · doi:10.18632/oncotarget.14012 · Cited by 319 · see citing works
Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer
Rowland, A., Dias, M. M., Wiese, M. D., Kichenadasse, G., McKinnon, R. A., Karapetis, C. S., & Sorich, M. J. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.173 · Cited by 319 · see citing works
Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial
Taı̈eb, J., Tabernero, J. M., Mini, E., Subtil, F., Folprecht, G., Laethem, J. V., Thaler, J., Bridgewater, J. A., Pétersen, L. N., Blons, H., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70227-x · Cited by 290 · see citing works
Self-citation
MicroRNA miR-183 Functions as an Oncogene by Targeting the Transcription Factor EGR1 and Promoting Tumor Cell Migration
Sarver, A. L., Li, L., & Subramanian, S. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2074 · Cited by 278 · see citing works
Pilot Trial of Combined BRAF and EGFR Inhibition in BRAF -Mutant Metastatic Colorectal Cancer Patients
Yaeger, R., Cercek, A., O'Reilly, E. M., Reidy, D. L., Kemeny, N., Wolinsky, T., Capanu, M., Gollub, M. J., Rosen, N., Berger, M. F., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2779 · Cited by 276 · see citing works
Heterogeneity in Colorectal Cancer: A Challenge for Personalized Medicine?
Molinari, C., Marisi, G., Passardi, A., Matteucci, L., De Maio, G., & Ulivi, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123733 · Cited by 262 · 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
Metastatic Colorectal Cancer: From Improved Survival to Potential Cure
Gallagher, D. J., & Kemeny, N. E. (2010) · Oncology · doi:10.1159/000315730 · Cited by 237 · see citing works
Clinical Implications of the Cancer Genome
MacConaill, L. E., & Garraway, L. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4944 · Cited by 228 · see citing works
Reply: Comment on ‘Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal-antibody therapy for RAS wild-type metastatic colorectal cancer’
Rowland, A., Dias, M. M., Wiese, M. D., Kichenadasse, G., McKinnon, R. A., Karapetis, C. S., & Sorich, M. J. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.325 · Cited by 228 · see citing works
The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-Analysis
Ardekani, G. S., Jafarnejad, S. M., Tan, L., Saeedi, A., & Li, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047054 · Cited by 224 · see citing works
Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?
Santini, D., Vincenzi, B., Addeo, R., Garufi, C., Masi, G., Scartozzi, M., Mancuso, A. P., Frezza, A. M., Venditti, O., Imperatori, M., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mdr623 · Cited by 211 · see citing works
Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab
Tol, J., Dijkstra, J. R., Klomp, M., Teerenstra, S., Dommerholt, M., Vink-Börger, M. E., van Cleef, P. H. J., van Krieken, J. H., Punt, C. J. A., & Nagtegaal, I. D. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.03.036 · Cited by 210 · see citing works
Impact of KRAS and BRAF Gene Mutation Status on Outcomes From the Phase III AGITG MAX Trial of Capecitabine Alone or in Combination With Bevacizumab and Mitomycin in Advanced Colorectal Cancer
Price, T. J., Hardingham, J. E., Lee, C. K., Weickhardt, A. J., Townsend, A. R., Wrin, J., Chua, A., Shivasami, A., Cummins, M. M., Murone, C., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.5520 · Cited by 210 · see citing works
The Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells
Cai, W.-Q., Zeng, L.-S., Wang, L., Wang, Y., Cheng, J.-T., Zhang, Y., Han, Z.-W., Zhou, Y., Huang, S.-L., Wang, X.-W., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01249 · Cited by 202 · see citing works
Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas
Anglesio, M. S., Kommoss, S., Tolcher, M. C., Clarke, B. A., Galletta, L., Porter, H., Damaraju, S., Fereday, S., Winterhoff, B. J. N., Kalloger, S. E., et al. (2012) · The Journal of Pathology · doi:10.1002/path.4088 · Cited by 198 · see citing works
Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases
Karagkounis, G., Torbenson, M. S., Daniel, H. D. J., Azad, N. S., Diaz, L. A., Donehower, R. C., Hirose, K., Ahuja, N., Pawlik, T. M., & Choti, M. A. (2013) · Cancer · doi:10.1002/cncr.28347 · Cited by 194 · see citing works
Oncogenic mutant forms of EGFR: Lessons in signal transduction and targets for cancer therapy
Pines, G., Köstler, W. J., & Yarden, Y. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.04.019 · Cited by 187 · see citing works
EGFR Signaling in Colorectal Carcinoma
Krasinskas, A. M. (2011) · Pathology Research International · doi:10.4061/2011/932932 · Cited by 186 · see citing works
HGF Rescues Colorectal Cancer Cells from EGFR Inhibition via MET Activation
Liska, D., Chen, C.-T., Bachleitner-Hofmann, T., Christensen, J. G., & Weiser, M. R. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0568 · Cited by 176 · see citing works
Changes in Colorectal Carcinoma Genomes under Anti-EGFR Therapy Identified by Whole-Genome Plasma DNA Sequencing
Mohan, S., Heitzer, E., Ulz, P., Lafer, I., Lax, S., Auer, M., Pichler, M., Gerger, A., Eisner, F., Höefler, G., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004271 · Cited by 175 · see citing works
Pragmatic issues in biomarker evaluation for targeted therapies in cancer
Gramont, A. D. E., Watson, S., Ellis, L. M., Rodon, J. A., Tabernero, J. M., de Gramont, A., & Hamilton, S. R. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.202 · Cited by 174 · see citing works
Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W. W., Cushman‐Vokoun, A. M., Funkhouser, W. K., Kopetz, S., Lieu, C. H., Lindor, N. M., Minsky, B. D., et al. (2017) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2016-0554-cp · Cited by 176 · see citing works
Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways
McCubrey, J. A., Steelman, L. S., Kempf, C., Chappell, W. H., Abrams, S. L., Stivala, F., Malaponte, G., Nicoletti, F., Libra, M., Bäsecke, J., et al. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22647 · Cited by 173 · see citing works
The current understanding on the impact of KRAS on colorectal cancer
Meng, M., Zhong, K., Jiang, T., Liu, Z., Kwan, H. Y., & Su, T. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111717 · Cited by 171 · see citing works
Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer
Dahabreh, I. J., Terasawa, T., Castaldi, P. J., & Trikalinos, T. A. (2011) · Annals of Internal Medicine · doi:10.7326/0003-4819-154-1-201101040-00006 · Cited by 169 · see citing works
Patient and Tumor Characteristics and BRAF and KRAS Mutations in Colon Cancer, NCCTG/Alliance N0147
Gonsalves, W. I., Mahoney, M. R., Sargent, D. J., Nelson, G. D., Alberts, S. R., Sinicrope, F. A., Goldberg, R. M., Limburg, P. J., Thibodeau, S. N., Grothey, A. F., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju106 · Cited by 169 · see citing works
MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A
Ohta, K., Hoshino, H., Wang, J., Ono, S., Iida, Y., Hata, K., Huang, S. K., Colquhoun, S. D., & Hoon, D. S. �. (2014) · Oncotarget · doi:10.18632/oncotarget.3085 · Cited by 167 · see citing works
Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: Analysis of data from the EXTREME and CRYSTAL studies
Licitra, L. F., Störkel, S., Kerr, K. M., Cutsem, E. V., Pirker, R., Hirsch, F. R., Vermorken, J. B., von Heydebreck, A., Esser, R., Celik, I., et al. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.11.018 · Cited by 167 · see citing works
A Review of the Most Promising Biomarkers in Colorectal Cancer: One Step Closer to Targeted Therapy
Deschoolmeester, V., Baay, M. F. D., Specenier, P. M., Lardon, F., & Vermorken, J. B. (2010) · The Oncologist · doi:10.1634/theoncologist.2010-0025 · Cited by 168 · see citing works
Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study
Kirzin, S., Marisa, L., Guimbaud, R., de Reyniès, A., Legrain, M., Laurent‐Puig, P., Cordelier, P., Pradère, B., Bonnet, D., Meggetto, F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103159 · Cited by 163 · see citing works
Self-citation
Functions and Regulation of the PTEN Gene in Colorectal Cancer
Molinari, F., & Frattini, M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2013.00326 · Cited by 162 · see citing works
Therapeutic targeting of epidermal growth factor receptor in human cancer: successes and limitations
Wykosky, J., Fenton, T. R., Furnari, F. B., & Cavenee, W. K. (2011) · 癌症：英文版 · doi:10.5732/cjc.010.10542 · Cited by 160 · see citing works
Acquired resistance to EGFR‐targeted therapies in colorectal cancer
Emburgh, B. O. V., Bianchi, A. S., Nicolantonio, F. D., Siena, S., & Bardelli, A. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.05.003 · Cited by 160 · see citing works
PIK3CA, BRAF, and PTEN Status and Benefit from Cetuximab in the Treatment of Advanced Colorectal Cancer—Results from NCIC CTG/AGITG CO.17
Karapetis, C. S., Jonker, D. J., Daneshmand, M., Hanson, J. E. L., O'Callaghan, C. J., Marginean, C. E., Zalcberg, J. R., Simes, J. R., Moore, M. J., Tebbutt, N. C., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0606 · Cited by 158 · see citing works
Cancer resistance to therapies against the EGFR-RAS-RAF pathway: The role of MEK
Martinelli, E., Morgillo, F., Troiani, T., & Ciardiello, F. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.12.001 · Cited by 156 · see citing works
Clinical Relevance of KRAS -Mutated Subclones Detected with Picodroplet Digital PCR in Advanced Colorectal Cancer Treated with Anti-EGFR Therapy
Laurent‐Puig, P., Pekin, D., Normand, C., Kotsopoulos, S. K., Nizard, P., Perez‐Toralla, K., Rowell, R. K., Olson, J., Srinivasan, P., Corre, D. L., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0983 · Cited by 156 · see citing works
Self-citation
PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response.
Liao, H.-W., Hsu, J.-M., Xia, W., Wang, H.-L., Wang, Y.-N., Chang, W.-C., Arold, S. T., Chou, C.-K., Tsou, P.-H., Yamaguchi, H., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci82826 · Cited by 155 · see citing works
Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial
Mulcahy, M. F., Mahvash, A., Pracht, M., Montazeri, A. H., Bandula, S., Martin, R. C. G., Herrmann, K., Brown, E., Zuckerman, D., Wilson, G., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.21.01839 · Cited by 156 · see citing works
Primary Colorectal Cancers and Their Subsequent Hepatic Metastases Are Genetically Different: Implications for Selection of Patients for Targeted Treatment
Vermaat, J. S. P., Nijman, I. J., Koudijs, M. J., Gerritse, F. L., Scherer, S. J., Mokrý, M., Roessingh, W. M., Lansu, N. R., de Bruijn, E., van Hillegersberg, R., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1965 · Cited by 153 · see citing works
Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells
Troiani, T., Martinelli, E., Napolitano, S., Vitagliano, D., Ciuffreda, L. P., Costantino, S., Morgillo, F., Capasso, A., Sforza, V., Nappi, A., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0423 · Cited by 150 · see citing works
Biomarkers in colorectal cancer: Current clinical utility and future perspectives
Vacante, M., Borzì, A. M., Basile, F., & Biondi, A. (2018) · World Journal of Clinical Cases · doi:10.12998/wjcc.v6.i15.869 · Cited by 150 · see citing works
Targeting the human EGFR family in esophagogastric cancer
Okines, A. F. C., Cunningham, D., & Chau, I. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.45 · Cited by 147 · see citing works
Molecular Biomarkers for the Evaluation of Colorectal Cancer
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W. W., Cushman‐Vokoun, A. M., Funkhouser, W. K., Kopetz, S., Lieu, C. H., Lindor, N. M., Minsky, B. D., et al. (2017) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.11.001 · Cited by 147 · see citing works
Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer
Kim, M. J., Lee, H. S., Kim, J. H., Kim, Y. J., Kwon, J. H., Lee, J., Bang, S., Park, K. U., Kim, D., Kang, S., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-347 · Cited by 141 · see citing works
Lynch Syndrome: An Updated Review
Sehgal, R., Sheahan, K. D., O’Connell, P. R., Hanly, A. M., Martin, S., & Winter, D. C. (2014) · Genes · doi:10.3390/genes5030497 · Cited by 140 · see citing works
A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy
Zhang, W., Winder, T., Ning, Y., Pohl, A. C., Yang, D., Kahn, M. R., Lurje, G., LaBonte, M. J., Wilson, P. M., Gordon, M. A., et al. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq315 · Cited by 137 · see citing works
Identification and characterization of EGF receptor in individual exosomes by fluorescence‐activated vesicle sorting
Higginbotham, J. N., Zhang, Q., Jeppesen, D. K., Scott, A. M., Manning, H. C., Ochieng, J., Franklin, J. L., & Coffey, R. J. (2016) · Journal of Extracellular Vesicles · doi:10.3402/jev.v5.29254 · Cited by 133 · see citing works
Implementing prognostic and predictive biomarkers in CRC clinical trials
Schaeybroeck, S. V., Allen, W. L., Turkington, R. C., & Johnston, P. G. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.15 · Cited by 126 · see citing works
Are KRAS/BRAF Mutations Potent Prognostic and/or Predictive Biomarkers in Colorectal Cancers?
Yokota, T. (2012) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/187152012799014968 · Cited by 127 · see citing works
Impact of KRAS, BRAF, PIK3CA Mutations, PTEN, AREG, EREG Expression and Skin Rash in ≥2nd Line Cetuximab-Based Therapy of Colorectal Cancer Patients
Saridaki, Z., Tzardi, M. N., Papadaki, C., Sfakianaki, M., Pega, F., Kalikaki, A., Tsakalaki, E., Trypaki, M., Messaritakis, I., Stathopoulos, E. N., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015980 · Cited by 127 · see citing works
Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study
Moehler, M. H., Mueller, A., Trarbach, T., Lordick, F., Seufferlein, T. T. W., Kubicka, S., Geißler, M., Schwarz, S., Galle, P. R., & Kanzler, S. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq591 · Cited by 124 · see citing works
mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1
Faber, A. C., Coffee, E. M., Costa, C., Dastur, A., Ebi, H., Hata, A. N., Yeo, A. T., Edelman, E. J., Song, Y., Tam, A. T., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0315 · Cited by 124 · see citing works
Molecular spectrum of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese colorectal cancer patients: analysis of 1,110 cases
Zhang, J., Zheng, J., Yang, Y., Lu, J., Gao, J., Lu, T., Sun, J. H., Jiang, H., Zhu, Y., Zheng, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep18678 · Cited by 124 · 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
Mechanisms of Innate and Acquired Resistance to Anti-EGFR Therapy: A Review of Current Knowledge with a Focus on Rechallenge Therapies
Parseghian, C. M., Napolitano, S., Loree, J. M., & Kopetz, S. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0823 · Cited by 121 · see citing works
Treatment of Unresectable and Metastatic Cutaneous Squamous Cell Carcinoma
Cranmer, L. D., Engelhardt, C., & Morgan, S. S. (2010) · The Oncologist · doi:10.1634/theoncologist.2009-0210 · Cited by 121 · see citing works
Translating cancer ‘omics’ to improved outcomes: Figure 1.Preprint
Vucic, E. A., Thu, K. L., Robison, K. E., Rybaczyk, L. A., Chari, R., Alvarez, C. E., & Lam, W. L. (2012) · Genome Research · doi:10.1101/gr.124354.111 · Cited by 120 · see citing works
IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies
Zanella, E. R., Galimi, F., Sassi, F., Migliardi, G., Cottino, F., Leto, S. M., Lupo, B., Erriquez, J., Isella, C., Comoglio, P. M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010445 · Cited by 117 · see citing works
Animal models of colorectal cancer
Johnson, R. L., & Fleet, J. C. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9404-6 · Cited by 119 · 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
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Authors: Laurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., Ducreux, M., Ychou, M., Bibeau, F., Bouché, O., Reid, J., Stone, S., & Penault-Llorca, F.
Affiliations: From the Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) -S775 Molecular Basis of Xenobiotics Response; Université Paris Descartes; Assistance Publique–Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hôpital Ambroise Paré, Paris; Centre Jean Perrin, Université d'Auvergne Equipe Associée EA4233 Centre Hospitalier Universitaire (CHU), Clermont-Ferrand; CHU, Tours; Institut Gustave Roussy, Villejuif; Centre Régional de Lutte contre le Cancer (CRLC) Val...
Inserm (FR)
ORCID: Cayre, Anne
Manceau, Gilles
Buc, Emmanuel
Bachet, Jean-Baptiste
Lecomte, Thierry
Boige, Valérie
Ducreux, Michel
Ychou, Marc
Bouché, Olivier
Stone, Steven
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2009-12-10
Volume: 27
Issue: 35
Pages: 5924-5930
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2008.21.6796
OpenAlex: W2125229905
Cited by: 673
References: 39
Citations by year: 2026: 2 · 2025: 10 · 2024: 16 · 2023: 6 · 2022: 10 · 2021: 22 · 2020: 16 · 2019: 27 · 2018: 26 · 2017: 32 · 2016: 45 · 2015: 55 · 2014: 81 · 2013: 73 · 2012: 85
FWCI: 41.77
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
HAL (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: cetuximab, metastatic colorectal cancer, KRAS wild-type, BRAF mutation, PTEN expression, EGFR amplification, predictive biomarkers, anti-EGFR antibody therapy, progression-free survival, overall survival, treatment response
MeSH terms: Cetuximab, Antibodies, Monoclonal, Antineoplastic Agents, France, Gene Amplification, Humans, Immunohistochemistry, Mutation, Predictive Value of Tests, Proto-Oncogene Proteins, Retrospective Studies, Time Factors, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), Treatment Outcome, In Situ Hybridization, In Situ Hybridization, Fluorescence, Risk Assessment, Disease-Free Survival, Patient Selection, ras Proteins, Proto-Oncogene Proteins B-raf, PTEN Phosphohydrolase, Kaplan-Meier Estimate, Precision Medicine, Antibodies, Monoclonal, Humanized, ErbB Receptors

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Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer

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