The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
A Molecularly Annotated Platform of Patient-Derived Xenografts (“Xenopatients”) Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer
Open accessPublished version of a preprint
Abstract
Only a fraction of patients with metastatic colorectal cancer receive clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) antibodies, which calls for the identification of novel biomarkers for better personalized medicine. We produced large xenograft cohorts from 85 patient-derived, genetically characterized metastatic colorectal cancer samples (“xenopatients”) to discover novel determinants of therapeutic response and new oncoprotein targets. Serially passaged tumors retained the morphologic and genomic features of their original counterparts. A validation trial confirmed the robustness of this approach: xenopatients responded to the anti-EGFR antibody cetuximab with rates and extents analogous to those observed in the clinic and could be prospectively stratified as responders or nonresponders on the basis of several predictive biomarkers. Genotype–response correlations indicated HER2 amplification specifically in a subset of cetuximab-resistant, KRAS/NRAS/BRAF/PIK3CA wild-type cases. Importantly, HER2 amplification was also enriched in clinically nonresponsive KRAS wild-type patients. A proof-of-concept, multiarm study in HER2-amplified xenopatients revealed that the combined inhibition of HER2 and EGFR induced overt, long-lasting tumor regression. Our results suggest promising therapeutic opportunities in cetuximab-resistant patients with metastatic colorectal cancer, whose medical treatment in the chemorefractory setting remains an unmet clinical need. Significance: Direct transfer xenografts of tumor surgical specimens conserve the interindividual diversity and the genetic heterogeneity typical of the tumors of origin, combining the flexibility of preclinical analysis with the informative value of population-based studies. Our suite of patient-derived xenografts from metastatic colorectal carcinomas reliably mimicked disease response in humans, prospectively recapitulated biomarker-based case stratification, and identified HER2 as a predictor of resistance to anti-epidermal growth factor receptor antibodies and of response to combination therapies against HER2 and epidermal growth factor receptor in this tumor setting. Cancer Discovery; 1(6); 508–23. ©2011 AACR. Read the Commentary on this article by Ciardiello and Normanno, p. 472 This article is highlighted in the In This Issue feature, p. 457
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“HER2 overexpression is a negative predictor associated with reduced efficacy of anti-EGFR therapy [31], and >36% of cetuximab-resistant mCRC with wild-type KRAS, NRAS, BRAF, and PI3K was found to display HER2 overexpression [32].”
From Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment (2024) · cites this paper as [32]
In the citing paper
“A series of studies have demonstrated that HER2 gene amplification or activating mutations can mediate resistance to anti-EGFR mAbs in CRC [27,178,179].”
From Drug Resistance in Colorectal Cancer: From Mechanism to Clinic (2022) · cites this paper as [27]
In the citing paper
“Preclinical studies have shown that the combination of HER2 and EGFR blockade can lead to CRC tumor regression [27,28,29].”
From Drug Resistance in Colorectal Cancer: From Mechanism to Clinic (2022) · cites this paper as [27]
In the citing paper
“Two independent studies have recently shown that HER2 amplification is a predictor of poor sensitivity to anti-EGFR antibodies [91, 92].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [91]
In the citing paper
“In retrospective studies, patients with tumors featuring HER2 amplification or heregulin overexpression and treated with cetuximab or panitumumab experienced disease progression and shorter progression-free and overall survival compared with HER2 wild-type cases [91-93].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [91]
In the citing paper
“only the dual targeting of HER2 and EGFR by combining a small-molecule inhibitor, such as the dual EGFR/HER2 inhibitor lapatinib, with a moAb, such as cetuximab or pertuzumab, induced overt and long-lasting tumor regressions in proof-of-concept trials in HER2-amplified xenopatients [91].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [91]
In the citing paper
“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 [91]
In the citing paper
“Strong preclinical evidence suggests that dual inhibition of ERBB2 is superior to monotherapy due to enhanced efficacy and reduced therapy resistance4648”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [46]
In the citing paper
“Bertotti et al. identified ERBB2 as a biomarker of resistance to anti-EGFR mAbs [113].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [113]
In the citing paper
“A total of 2–7% of unselected CRCs were found to have ERBB2/mutations, and this number was much higher in KRAS wild-type cases (13.6%) and in KRAS/NRAS/BRAF/PIK3CA quadruple wild-type cases (36% )[13, 113, 114].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [113]
In the citing paper
“Finally, using patient-derived colon cancer xenografts, Bertotti et al. identified HER2 gene amplification as a predictor of resistance to cetuximab among KRAS wild-type tumors (Bertotti et al., 2011).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Bertotti et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Self-citationCetuximab 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
ERBB receptors and cancer: the complexity of targeted inhibitors
Hynes, N. E., & Lane, H. A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1609 · Cited by 3,379
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
Self-citationUmar, A., Boland, C. R., Terdiman, J. P., Syngal, S., de la Chapelle, A., Rüschoff, J., Fishel, R. A., Lindor, N. M., Burgart, L. J., Hamelin, R., et al. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh034 · Cited by 3,181
The Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833
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-citationVan 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
Self-citationCetuximab for the Treatment of Colorectal Cancer
Jonker, D. J., O'Callaghan, C. J., Karapetis, C. S., Zalcberg, J. R., Tu, D., Au, H.-J., Berry, S. R., Krahn, M., Price, T., Simes, R. J., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071834 · Cited by 1,904
Cited by
Sorted by citations
Items 301–400 of 944
Molecular subtypes and the evolution of treatment management in metastatic colorectal cancer
Martini, G., Dienstmann, R., Ros, J., Baraibar, I., Cuadra‐Urteaga, J. L., Salvà, F., Ciardiello, D., Mulet-Margalef, N., Argilés, G., Tabernero, J. M., et al. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835920936089 · Cited by 57
Experimental mouse models for translational human cancer research
Zhou, Y., Xia, J., Xu, S., She, T., Zhang, Y., Sun, Y., Wen, M., Jiang, T., Xiong, Y., & Lei, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1095388 · Cited by 52
HER2 as a Predictive Biomarker and Treatment Target in Colorectal Cancer
Cuyper, A. D., den Eynde, M. V., & Machiels, J. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2020.02.007 · Cited by 51
MACC1 mRNA Levels Predict Cancer Recurrence After Resection of Colorectal Cancer Liver Metastases
Isella, C., Mellano, A., Galimi, F., Petti, C., Capussotti, L., Simone, M. D., Bertotti, A., Médico, E., & Muratore, A. (2013) · Annals of Surgery · doi:10.1097/sla.0b013e31828f96bc · Cited by 48
Self-citationHER2 in Solid Tumors: More than 10 Years Under the Microscope; where are we now?
Martin, V., Cappuzzo, F., Mazzucchelli, L., & Frattini, M. (2014) · Future Oncology · doi:10.2217/fon.14.19 · Cited by 48
Choosing wisely – Preclinical test models in the era of precision medicine
Klinghammer, K. F., Walther, W., & Hoffmann, J. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.02.009 · Cited by 50
Liu, Z., Zhang, Y., Dang, Q., Wu, K., Jiao, D., Li, Z., Sun, Z., & Han, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.632430 · Cited by 48
Comprehensive review of the resistance mechanisms of colorectal cancer classified by therapy type
Oh, J. M., Kim, S. W., Tsung, C., Kent, E. W., Jain, A., Ruff, S. M., & Zhang, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1571731 · Cited by 50
Shen, L., Li, Z., Guo, T., Xing, X., Cheng, X., Du, H., Wen, X., & Ji, J. (2015) · Oncotarget · doi:10.18632/oncotarget.6673 · Cited by 47
Chen, J., Jin, Y., Zhai, Y., Qiong, Q., & Zhou, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10151 · Cited by 46
Patient-Derived Xenograft Models for Endometrial Cancer Research
Moiola, C. P., López-Gil, C., Cabrera, S., García, Á., Nyen, T. V., Annibali, D., Fonnes, T., Vidal, A., Villanueva, A., Matías‐Guiu, X., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082431 · Cited by 49
Cetuximab as a Key Partner in Personalized Targeted Therapy for Metastatic Colorectal Cancer
Gonzalez, N. S., Ros, J., Baraibar, I., Salvà, F., Rodríguez-Castells, M., Alcaráz, A., García, A., Tabernero, J. M., & Élez, E. (2024) · Cancers · doi:10.3390/cancers16020412 · Cited by 50
Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours
Martín, V., Chiriaco, C., Modica, C., Acquadro, A., Cortese, M., Galimi, F., Perera, T. P. S., Gammaitoni, L., Aglietta, M., Comoglio, P. M., et al. (2019) · British Journal of Cancer · doi:10.1038/s41416-018-0315-3 · Cited by 46
Self-citationPark, S., Hwang, C. Y., Cho, S., Lee, D., Gong, J., Lee, S., Nam, S., & Cho, K. (2019) · FEBS Journal · doi:10.1111/febs.14773 · Cited by 47
A Genomic Analysis Workflow for Colorectal Cancer Precision Oncology
Corti, G., Bartolini, A., Crisafulli, G., Novara, L., Rospo, G., Montone, M., Negrino, C., Mussolin, B., Buscarino, M., Isella, C., et al. (2019) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2019.02.008 · Cited by 45
Self-citationMolecular pathways: sensitivity and resistance to anti-EGFR antibodies
Bertotti, A., & Sassi, F. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0848 · Cited by 45
Self-citationGenetic Alterations of Metastatic Colorectal Cancer
Testa, U., Castelli, G., & Pelosi, E. (2020) · Biomedicines · doi:10.3390/biomedicines8100414 · Cited by 44
Circulating tumour DNA, a promising biomarker for the management of colorectal cancer
Khakoo, S. S., Georgiou, A., Gerlinger, M., Cunningham, D., & Starling, N. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.12.002 · Cited by 47
Chamberlain, C. E., German, M. S., Yang, K. Y., Wang, J., VanBrocklin, H. F., Regan, M., Shokat, K. M., Ducker, G. S., Kim, G., Hann, B. C., et al. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-1204 · Cited by 45
Inoue, A., Deem, A. K., Kopetz, S., Heffernan, T. P., Draetta, G. F., & Carugo, A. (2019) · Cancers · doi:10.3390/cancers11091321 · Cited by 46
Mullins, C. S., Micheel, B., Matschos, S., Leuchter, M., Bürtin, F., Krohn, M., Hühns, M., Klar, E., Prall, F., & Linnebacher, M. (2019) · Cancers · doi:10.3390/cancers11101520 · Cited by 45
Al-Kabani, A., Huda, B., Haddad, J., Yousuf, M., Bhurka, F., Ajaz, F., Patnaik, R., Jannati, S., & Banerjee, Y. (2025) · Cancers · doi:10.3390/cancers17132163 · Cited by 53
Arcaroli, J. J., Tai, W., McWilliams, R. R., Bagby, S. M., Blatchford, P. J., Varella‐Garcia, M., Purkey, A., Quackenbush, K. S., Song, E., Pitts, T. M., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.29676 · Cited by 44
Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
Moro, M., Bertolini, G., Caserini, R., Borzi, C., Boeri, M., Fabbri, A., Leone, G., Gasparini, P., Galeone, C., Pelosi, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-06912-7 · Cited by 44
HER2-targeted therapy: an emerging strategy in advanced colorectal cancer
Salvia, A. L., López-Gómez, V., & García‐Carbonero, R. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1555583 · Cited by 44
Zhang, H., Liu, R., Yan, C., Liu, L., Tong, Z., Jiang, W., Yao, M., Fang, W. J., & Chen, Z. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.11.015 · Cited by 45
Wang, G., He, Y., Sun, Y., Wang, W., Qian, X., Yu, X., & Pan, Y. (2019) · Clinical & Translational Oncology · doi:10.1007/s12094-019-02213-9 · Cited by 45
Early-onset cancers: Biological bases and clinical implications
Mauri, G., Patelli, G., Bianchi, A. S., Abrignani, S., Bodega, B., Marsoni, S., Costanzo, V., Bachi, A., Siena, S., & Bardelli, A. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101737 · Cited by 51
Self-citationSeol, H. S., Kang, H.-J., Lee, S.-I., Kim, N. E., Kim, T., Chun, S., Kim, T. W., Yu, C. S., Suh, Y., Singh, S. R., et al. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.11.010 · Cited by 43
Suetsugu, A., Katz, M. H. G., Fleming, J. B., Truty, M. J., Thomas, R. M., Saji, S., Moriwaki, H., Bouvet, M., & Hoffman, R. M. (2012) · PubMed · Cited by 43
Cavalloni, G., Neia, C. P., Sassi, F. P., Chiorino, G., Sarotto, I., Aglietta, M., & Leone, F. (2016) · BMC Cancer · doi:10.1186/s12885-016-2136-1 · Cited by 42
Self-citationCapturing colorectal cancer inter‐tumor heterogeneity in patient‐derived xenograft (PDX) models
Prasetyanti, P. R., van Hooff, S. R., van Herwaarden, T., de Vries, N., Kalloe, K., Rodermond, H. M., van Leersum, R., de Jong, J. H., Franitza, M., Nürnberg, P., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31767 · Cited by 43
Lu, M., Sanderson, S. M., Zessin, A. S., Ashcraft, K. A., Jones, L. W., Dewhirst, M. W., Locasale, J. W., & Hsu, D. S. (2018) · Cancer & Metabolism · doi:10.1186/s40170-018-0190-7 · Cited by 43
Johnson, R. M., Qu, X., Lin, C.-F., Huw, L.-Y., Venkatanarayan, A., Sokol, E., Ou, F.-S., Ihuegbu, N., Zill, O. A., Kabbarah, O., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33172-5 · Cited by 42
Yao, Y., Wang, Y., Chen, L., Tian, Z., Yang, G., Wang, R., Wang, C., Wu, Q., Wu, Y., Gao, J., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00908-0 · Cited by 44
Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice
Chen, A., Neuwirth, I., & Herndler‐Brandstetter, D. (2023) · Cancers · doi:10.3390/cancers15112989 · Cited by 44
Advancing translational research for colorectal immuno-oncology
Thomas, E., Wright, J. A., Blake, S. J., Page, A. J., Worthley, D. L., & Woods, S. L. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02392-x · Cited by 44
Jeong, J. H., Kim, J., Hong, Y. S., Kim, D., Kim, J. E., Kim, S. Y., Kim, K., Yoon, Y., Kim, D., Chun, S., et al. (2017) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2017.01.005 · Cited by 43
Rachiglio, A. M., Lambiase, M., Fenizia, F., Roma, C., Cardone, C., Iannaccone, A., Luca, A. D., Carotenuto, M., Frezzetti, D., Martinelli, E., et al. (2019) · Cancers · doi:10.3390/cancers11060859 · Cited by 43
Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer
Zhou, Q. X., Perakis, S. O., Ulz, P., Mohan, S., Riedl, J. M., Talakić, E., Lax, S., Tötsch, M., Höefler, G., Bauernhofer, T., et al. (2020) · Genome Medicine · doi:10.1186/s13073-020-0719-6 · Cited by 43
Patient-Derived In Vitro Models for Drug Discovery in Colorectal Carcinoma
Ramzy, G. M., Koessler, T., Ducrey, E., McKee, T., Ris, F., Buchs, N. C., Rubbia‐Brandt, L., Dietrich, P., & Nowak-Sliwinska, P. M. (2020) · Cancers · doi:10.3390/cancers12061423 · Cited by 45
HER2 targeted therapy in colorectal cancer: New horizons
Suwaidan, A. A., Lau, D. K., & Chau, I. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102363 · Cited by 45
Colorectal Cancer: From Genetic Landscape to Targeted Therapy
Bali, M. E., Bakkach, J., & Mechita, M. B. (2021) · Journal of Oncology · doi:10.1155/2021/9918116 · Cited by 43
Understanding resistance to targeted cancer drugs through loss of function genetic screens
Berns, K., & Bernards, R. (2012) · Drug Resistance Updates · doi:10.1016/j.drup.2012.10.002 · Cited by 41
Role of HGF–MET Signaling in Primary and Acquired Resistance to Targeted Therapies in Cancer
Corte, C. M. D., Fasano, M., Papaccio, F., Ciardiello, F., & Morgillo, F. (2014) · Biomedicines · doi:10.3390/biomedicines2040345 · Cited by 41
Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer
Shimada, Y., Yagi, R., Kameyama, H., Nagahashi, M., Ichikawa, H., Tajima, Y., Okamura, T., Nakano, M., Nakano, M., Sato, Y., et al. (2017) · Human Pathology · doi:10.1016/j.humpath.2017.02.004 · Cited by 41
Role of Biologics in First-Line Treatment of Colorectal Cancer
Mahipal, A., & Grothey, A. F. (2016) · Journal of Oncology Practice · doi:10.1200/jop.2016.018382 · Cited by 42
Lallo, A., Gulati, S., Schenk, M. W., Khandelwal, G., Berglund, U. W., Pateras, I. S., Chester, C., Pham, T. M., Kalderén, C., Frese, K. K., et al. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14542 · Cited by 40
HER2 Amplification and Anti-EGFR Sensitivity in Advanced Colorectal Cancer
Bregni, G., Sciallero, S., & Sobrero, A. F. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2018.7229 · Cited by 40
Modeling rectal cancer to advance neoadjuvant precision therapy
Janakiraman, H., Zhu, Y., Becker, S. A., Wang, C., Cross, A. W., Curl, E., Lewin, D., Hoffman, B. J., Warren, G. W., Hill, E. G., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.32876 · Cited by 40
Dienstmann, R., Salazar, R., & Tabernero, J. (2014) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2014.34.91 · Cited by 38
Current and emerging concepts for systemic treatment of metastatic colorectal cancer
Steup, C., Kennel, K. B., Neurath, M. F., Fichtner-Feigl, S., & Greten, F. R. (2025) · Gut · doi:10.1136/gutjnl-2025-335412 · Cited by 39
Ciracì, P., Studiale, V., Taravella, A., Antoniotti, C., & Cremolini, C. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00965-0 · Cited by 47
Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors.
Luo, M., & Fu, L.-W. (2014) · Europe PMC (PubMed Central) · Cited by 38
Chou, J., Fitzgibbon, M., Mortales, C., Towlerton, A. M. H., Upton, M. P., Yeung, R. S. W., McIntosh, M. W., & Warren, E. H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079874 · Cited by 39
Bianchi, A. S., Fieuws, S., Veronese, S. M., Moroni, M., Personeni, N., Frattini, M., Torri, V., Cappuzzo, F., Borght, S. V., Martin, V., et al. (2011) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2011-200353 · Cited by 40
Self-citationCurrent and future biomarkers in the treatment of colorectal cancer
Cuyle, P.-J. A., & Prenen, H. (2016) · Acta Clinica Belgica · doi:10.1080/17843286.2016.1262996 · Cited by 40
Gutierrez, M. E., Price, K. S., Lanman, R. B., Nagy, R. J., Shah, I., Mathura, S., Mulcahy, M., Norden, A. D., & Goldberg, S. L. (2019) · JCO Precision Oncology · doi:10.1200/po.19.00274 · Cited by 39
Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer
Guarini, C., Grassi, T., Pezzicoli, G., & Porta, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136813 · Cited by 41
Fanotto, V., Ongaro, E., Rihawi, K., Avallone, A., Silvestris, N., Fornaro, L., Vasile, E., Antonuzzo, L., Leone, F., Rosati, G., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11264 · Cited by 39
Translation Potential and Challenges of In Vitro and Murine Models in Cancer Clinic
Long, Y., Xie, B., Shen, H. C., & Wen, D. (2022) · Cells · doi:10.3390/cells11233868 · Cited by 43
Asić, K. (2015) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2015.08.004 · Cited by 38
Targeting HPV16 DNA Using CRISPR/Cas Inhibits Anal Cancer Growth in Vivo
Hsu, D. S., Kornepati, A. V. R., Glover, W., Kennedy, E. M., & Cullen, B. R. (2018) · Future Virology · doi:10.2217/fvl-2018-0010 · Cited by 38
Izar, B., Rotow, J. K., Gainor, J. F., Clark, J. W., & Chabner, B. A. (2013) · Pharmacological Reviews · doi:10.1124/pr.113.007807 · Cited by 38
Loree, J. M., Kopetz, S., & Raghav, K. P. S. (2017) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo.2017.01.01 · Cited by 36
Ponterio, E., Maria, R. D., & Haas, T. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.565631 · Cited by 37
Bekaii-Saab, T. S., Lach, K., Hsu, L.-I., Siadak, M., Stecher, M., Ward, J., Beckerman, R., & Strickler, J. H. (2023) · The Oncologist · doi:10.1093/oncolo/oyad200 · Cited by 36
Ciardiello, F., & Normanno, N. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0261 · Cited by 36
Sereti, E., Karagianellou, T., Kotsoni, I., Magouliotis, D. E., Kamposioras, K. V., Ulukaya, E., Sakellaridis, N., Zacharoulis, D., & DIMAS, K. S. (2018) · Journal of Proteomics · doi:10.1016/j.jprot.2018.01.012 · Cited by 37
Dzobo, K., Rowe, A., Senthebane, D. A., AlMazyadi, M., Patten, V. A., & Parker, M. I. (2018) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2018.0172 · Cited by 37
Spagnol, G., Sensi, F., Tommasi, O. D., Marchetti, M., Bonaldo, G., Xhindoli, L., Noventa, M., Agostini, M., Tozzi, R., & Saccardi, C. (2023) · Cancers · doi:10.3390/cancers15072059 · Cited by 38
Beekhof, R., Bertotti, A., Böttger, F., Vurchio, V., Cottino, F., Zanella, E. R., Migliardi, G., Viviani, M., Grassi, E., Lupo, B., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abm3687 · Cited by 37
Self-citationBelli, V., Matrone, N., Napolitano, S., Migliardi, G., Cottino, F., Bertotti, A., Trusolino, L., Martinelli, E., Morgillo, F., Ciardiello, D., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1230-z · Cited by 36
Self-citationPrognostic Value and Molecular Landscape of HER2 Low-Expressing Metastatic Colorectal Cancer
Yagisawa, M., Sawada, K., Nakamura, Y., Fujii, S., Yuki, S., Komatsu, Y., Yoshino, T., Sakamoto, N., & Taniguchi, H. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2020.11.002 · Cited by 36
Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers
Hwang, K., Yoon, J. H., Lee, J., & Lee, S. (2021) · Biomedicines · doi:10.3390/biomedicines9010039 · Cited by 37
Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review
DeStefanis, R. A., Kratz, J. D., Emmerich, P. B., & Deming, D. A. (2019) · Current Colorectal Cancer Reports · doi:10.1007/s11888-019-00430-6 · Cited by 34
The role of personalized medicine in metastatic colorectal cancer: an evolving landscape
Moorcraft, S. Y., Smyth, E. C., & Cunningham, D. (2013) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x13491797 · Cited by 35
LAS: A Software Platform to Support Oncological Data Management
Baralis, E., Bertotti, A., Fiori, A., & Grand, A. (2012) · Journal of Medical Systems · doi:10.1007/s10916-012-9891-6 · Cited by 34
Self-citationLessons Learned from Radiation Oncology Clinical Trials
Liu, F., participants, F. T. W., Okunieff, P. G., Bernhard, E. J., Stone, H. B., Yoo, S. S., Coleman, C. N., Vikram, B., Brown, M., Buatti, J. M., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1116 · Cited by 34
Hsu, D. S., Hwang, W., Yuh, C., Chu, C.-H., Ho, Y.-H., Chen, P.-B., Lin, H.-S., Lin, H., Wu, S.-P., Lin, C.-Y., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1955 · Cited by 34
Tashiro, T., Okuyama, H., Endo, H., Kawada, K., Ashida, Y., Ohue, M., Sakai, Y., & Inoue, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174151 · Cited by 31
Targeting HER 2 in patient‐derived xenograft ovarian cancer models sensitizes tumors to chemotherapy
Harris, F. R., Zhang, P., Yang, L., Hou, X., Leventakos, K., Weroha, S. J., Vasmatzis, G., & Kovtun, I. V. (2018) · Molecular Oncology · doi:10.1002/1878-0261.12414 · Cited by 34
Investigational multitargeted kinase inhibitors in development for head and neck neoplasms
Šola, A. M., Johnson, D. E., & Grandis, J. R. (2019) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1581172 · Cited by 34
Battaglin, F., Puccini, A., Djaballah, S. A., & Lenz, H. (2019) · Cancer Management and Research · doi:10.2147/cmar.s186042 · Cited by 36
Nowak, J. A. (2020) · Surgical pathology clinics · doi:10.1016/j.path.2020.05.007 · Cited by 35
Targeting HER2 genomic alterations in non-small cell lung cancer
Zeng, J., Ma, W., Young, R. B., & Li, T. (2021) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2021.04.001 · Cited by 37
Current concepts of anti-EGFR targeting in metastatic colorectal cancer
Doleschal, B., Petzer, A., & Rumpold, H. F. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1048166 · Cited by 36
Sclafani, F., Roy, A., Cunningham, D., Wotherspoon, A., Peckitt, C., Gonzalez de Castro, D., Tabernero, J., Glimelius, B., Cervantes, A., Eltahir, Z., et al. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt408 · Cited by 33
Wensink, G. E., Bond, M. J. G., Küçükköse, E., May, A. M., Vink, G. R., Koopman, M., Kranenburg, O., & Roodhart, J. M. L. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102174 · Cited by 35
Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis
Chen, C., Wang, X., Xiong, X., Liu, Q., Huang, Y., Xu, Q., Hu, J., Ge, G., & Ling, K. (2014) · Oncogene · doi:10.1038/onc.2014.393 · Cited by 32
MET-Mediated Resistance to EGFR Inhibitors: An Old Liaison Rooted in Colorectal Cancer Stem Cells
Boccaccio, C., Luraghi, P., & Comoglio, P. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1088 · Cited by 34
Self-citationMartinelli, E., Troiani, T., Sforza, V., Martini, G., Cardone, C., Vitiello, P. P., Ciardiello, D., Rachiglio, A. M., Normanno, N., Bianchi, A. S., et al. (2018) · ESMO Open · doi:10.1136/esmoopen-2017-000299 · Cited by 34
Self-citationUpdate on systemic therapy for colorectal cancer: biologics take sides
Gbolahan, O. B., & O’Neil, B. H. (2019) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2019.01.12 · Cited by 33
Chang, J., Xu, M., Wang, C., Huang, D., Zhang, Z., Chen, Z., Zhu, X., & Li, W. (2022) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2022.07.003 · Cited by 35
Lee, M. S., & Kopetz, S. (2015) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2015.05.006 · Cited by 33
Cortese, M., Torchiaro, E., D'Andrea, A., Petti, C., Invrea, F., Franco, L., Donini, C., Leuci, V., Leto, S. M., Vurchio, V., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.06.023 · Cited by 35
Self-citationApicella, M., Migliore, C., Capelôa, T., Menegon, S., Cargnelutti, M., Degiuli, M., Sapino, A., Sottile, A., Sarotto, I., Casorzo, L., et al. (2016) · Oncogene · doi:10.1038/onc.2016.283 · Cited by 32
Self-citationAdvances in Modeling the Immune Microenvironment of Colorectal Cancer
Yoon, P., Piccolo, N. D., Shirure, V. S., Peng, Y., Kirane, A., Canter, R. J., Fields, R. C., George, S. C., & Gholami, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.614300 · Cited by 33
Characterization of the large‐scale Japanese patient‐derived xenograft (J‐PDX) library
Yagishita, S., Kato, K., Takahashi, M., Imai, T., Yatabe, Y., Kuwata, T., Suzuki, M., Ochiai, A., Ohtsu, A., Shimada, K., et al. (2021) · Cancer Science · doi:10.1111/cas.14899 · Cited by 32
Affolter, A., Lammert, A., Kern, J., Scherl, C., & Rotter, N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.666515 · Cited by 34
Metadata
- Authors
- Bertotti, A., Migliardi, G., Galimi, F., Sassi, F., Torti, D., Isella, C., Corà, D., Di Nicolantonio, F., Buscarino, M., Petti, C., Ribero, D., Russolillo, N., Muratore, A., Massucco, P., Pisacane, A., Molinaro, L., Valtorta, E., Sartore-Bianchi, A., Risio, M., Capussotti, L., Gambacorta, M., Siena, S., Medico, E., Sapino, A., Marsoni, S., Comoglio, P. M., Bardelli, A., & Trusolino, L.
- Affiliations
- IFOM (IT)
- Authors' Affiliations: 1Laboratory of Molecular Pharmacology, 2Laboratory of Oncogenomics, 3Laboratory of Systems Biology, 4Laboratory of Molecular Genetics, 5Division of Surgical Oncology, 6Unit of Pathology, 7Clinical Coordination Unit, and 8Molecular Clinical Oncology, Institute for Cancer Research and Treatment, Torino; Departments of 9Oncological Sciences and 10Biomedical Sciences and Human Oncology, University of Torino Medical School, Torino; 11Department of Surgery, Mauriziano Umberto I Hospital, Torino; 12FIRC Institute of Molecular Oncology, Milano; 13Division of Pathology, 14Falck Division of Medical Oncology, Ospedale Niguarda Ca' Granda, Milano; and 15Southern Europe New Drug Organization Foundation, Milano, Italy
- ORCID
- Venue
- Cancer Discovery
- Published
- 2011-11-01
- Volume
- 1
- Issue
- 6
- Pages
- 508-523
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W1987443121
- Cited by
- 939
- References
- 56
- Citations by year
- 2026: 24 · 2025: 42 · 2024: 46 · 2023: 79 · 2022: 72 · 2021: 74 · 2020: 71 · 2019: 86 · 2018: 86 · 2017: 90 · 2016: 71 · 2015: 62 · 2014: 60 · 2013: 48 · 2012: 23
- FWCI
- 21.44
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- Regione Piemonte
- Genentech
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- patient-derived xenografts, metastatic colorectal cancer, cetuximab resistance, HER2 amplification, anti-EGFR therapy, predictive biomarkers, combination therapy, KRAS wild-type, BRAF wild-type, treatment resistance, tumor heterogeneity
- MeSH terms
- Cetuximab, Aged, Aged, 80 and over, Animals, Antibodies, Monoclonal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Prospective Studies, Biomarkers, Tumor, Colorectal Neoplasms, ras Proteins, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Mice, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
