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Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Open accessAbstract
A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers. After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug. The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood. Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance.
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In the citing paper
“Patients who initially respond to anti-EGFR develop acquired resistance within 12 to 18 months due to secondary mutations in KRAS genes, EGFR exodomain alteration, and clonal selection [9].”
From Overcoming Resistance to Anti-EGFR Therapies: Mechanisms of Cetuximab and Panitumumab Resistance and Emerging Combination Strategies (2026) · cites this paper as [9]
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In the citing paper
“We and others previously reported that KRAS acquired mutations are responsible for secondary resistance to anti-EGFR therapies in CRC(22, 23).”
From EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer. (2020) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“Patients who fail to respond to therapy initially exhibit intrinsic resistance, whereas those who relapse after initial response are associated with acquired resistance [9].”
From Overcoming Resistance to Anti-EGFR Therapies: Mechanisms of Cetuximab and Panitumumab Resistance and Emerging Combination Strategies (2026) · cites this paper as [9]
In the citing paper
“Emergence of KRAS amplification and acquisition of secondary KRAS mutations (G12C, G12D, G13D and Q61H) was detected as one mechanism of acquired resistance in metastatic CRC patients, who relapsed on cetuximab or panitumumab treatment (78, 79).”
From Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants (2022) · cites this paper as [78]
In the citing paper
“KRAS point mutations and gene copy number gains are responsible not only for primary but also for acquired resistance in 38–60 % of patients who relapse on cetuximab or panitumumab [37-39].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [38]
In the citing paper
“KRAS alterations could be identified noninvasively 5–10 months before radiographic disease progression by analyzing cell-free circulating tumor DNA (ctDNA) [37, 38].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [38]
In the citing paper
“however, the proof of principle that such an approach could complement tumor biopsy and provide an early warning of acquired resistance has been established [38, 41, 136].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [38]
In the citing paper
“To address these challenges, Mirati Therapeutics conducted high-resolution crystal structure analyses of compounds bound to mutant KRAS proteins, optimizing these compounds to develop MRTX1133, a non-covalent, selective inhibitor for KRAS G12D [60].”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [60]
In the citing paper
“For instance, BRAF (V600E) and MAP2K1/MEK1 (K57T, K57N, I99_K104 deletion, and E102_I103 deletion) can also cause acquired drug resistance [94, 108–111].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [110]
In the citing paper
“By performing repeat biopsies and evaluating circulating tumor DNA, investigators observed the emergence of KRAS mutations as a resistance mechanism (Diaz et al., 2012; Misale et al., 2012).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Misale et al., 2012
In the citing paper
“non-invasive measures such as molecular interrogation of circulating tumor cells or plasma DNA may help capture the heterogeneity of resistance in patients, as was done to identify the development of KRAS mutations in colorectal cancers that acquire resistance to cetuximab (Diaz et al., 2012; Misale et al., 2012).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Misale et al., 2012
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Citations
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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
Self-citationCirculating mutant DNA to assess tumor dynamics
Diehl, F., Schmidt, K., Choti, M. A., Romans, K. E., Goodman, S. N., Li, M., Thornton, K. A., Agrawal, N., Sokoll, L. J., Szabo, S., et al. (2008) · Nature Medicine · doi:10.1038/nm.1789 · Cited by 2,746
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
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
Self-citationMolecular 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-citationActivation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab
Yonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002442 · Cited by 663
Arcila, M. E., Oxnard, G. R., Nafa, K., Riely, G. J., Solomon, S. B., Zakowski, M. F., Kris, M. G., Pao, W., Miller, V. A., & Ladanyi, M. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2277 · Cited by 574
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Sriraman, S. K., Geraldo, V. P. N., Luther, E., Degterev, A., & Torchilin, V. P. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.10.037 · Cited by 28
Pietrantonio, F., Perrone, F., Biondani, P., Maggi, C., Lampis, A., Bertan, C. M., Venturini, F., Tondulli, L., Ferrari, D., Ricci, V., et al. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.26343 · Cited by 28
Sylvester, B. E., & Vakiani, E. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2078-6891.2015.083 · Cited by 28
Self-citationHata, T., Mokutani, Y., Takahashi, H., Inoue, A., Munakata, K., Nagata, K., Haraguchi, N., Nishimura, J., Hata, T., Matsuda, C., et al. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3813 · Cited by 28
Huth, H. W., Santos, D. M., Gravina, H. D., Resende, J. M., Goes, A. M., de Lima, M. E., & Ropert, C. (2017) · Oncology Reports · doi:10.3892/or.2017.5452 · Cited by 28
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Zhou, M., Niu, H., Cui, D., Xu, M., Li, J., Huang, G., Zhou, M., Xiong, C., Liu, Y., Xu, X., et al. (2026) · Molecular Cancer · doi:10.1186/s12943-025-02557-7 · Cited by 27
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Deipolyi, A. R., Zhang, Y. S., Khademhosseini, A., Naidu, S., Borad, M. J., Şahin, B., Mathur, A. K., & Öklü, R. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6030026 · Cited by 27
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Cox, V. L., Bhosale, P., Varadhachary, G. R., Wagner‐Bartak, N. A., Glitza, I. C., Gold, K. A., Atkins, J. T., Soliman, P. T., Hong, D. S., & Qayyum, A. (2017) · Radiology · doi:10.1148/radiol.2017152224 · Cited by 27
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Shu, L., Wang, D., Saba, N. F., & Chen, Z. G. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0660 · Cited by 27
Yamada, T., Matsuda, A., Takahashi, G., Iwai, T., Takeda, K., Ueda, K., Kuriyama, S., Koizumi, M., Shinji, S., Yokoyama, Y., et al. (2020) · International Journal of Clinical Oncology · doi:10.1007/s10147-020-01691-0 · Cited by 27
Nicolazzo, C., Barault, L., Caponnetto, S., Renzi, G. D., Belardinilli, F., Bottillo, I., Bargiacchi, S., Macagno, M., Grammatico, P., Giannini, G., et al. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.03.014 · Cited by 27
Zhang, K., Rodriguez, L., Cheng, L. Y., Wang, M., & Zhang, D. Y. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c03716 · Cited by 27
Self-cascade nanohybrids boost cell ferroptosis stress for tumor radiosensitization therapy
Wu, Q., Hou, M., Zhang, P., Jiang, Y., Liu, M., Xiong, L., Hai, W., Zhang, M., Li, X., Li, B., et al. (2022) · Applied Materials Today · doi:10.1016/j.apmt.2022.101558 · Cited by 28
Zhang, Q., Zheng, Y., Liu, J., Tang, X., Wang, Y., Li, X., Li, H., Zhou, X., Tang, S., Tang, Y., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-022-05536-8 · Cited by 27
Synthetic sickness or lethality points at candidate combination therapy targets in glioblastoma
Szczurek, E., Misra, N., & Vingron, M. (2013) · International Journal of Cancer · doi:10.1002/ijc.28235 · Cited by 27
Spectrum of Gene Mutations in Colorectal Cancer
Dienstmann, R., & Tabernero, J. M. (2016) · The Cancer Journal · doi:10.1097/ppo.0000000000000191 · Cited by 27
Kim, K., Kim, J., Hong, Y. S., Ahn, S., Chun, S., Hong, S., Jang, S. J., Yu, C. S., Kim, J. C., & Kim, T. W. (2016) · Cancer Research and Treatment · doi:10.4143/crt.2015.490 · Cited by 27
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Briffa, R., Langdon, S. P., Grech, G., & Harrison, D. J. (2018) · InTech eBooks · doi:10.5772/intechopen.70781 · Cited by 27
Potential clinical applications of circulating cell-free DNA in ovarian cancer patients
Barbosa, A. P. F., Peixoto, A., Pinto, P., Pinheiro, M., & Teixeira, M. R. (2018) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2018.5 · Cited by 27
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Saliani, M., Jalal, R., & Ahmadian, M. R. (2019) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2018.0530 · Cited by 27
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Song, C. M., Kong, Y., Huang, L., Luo, H., & Zhu, X. M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110445 · Cited by 27
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Zahrani, A., Kandil, M. S., Badar, T., Abdelsalam, M. G. A., Al-Faiar, A., & Ismail, A. A. (2014) · Tumori Journal · doi:10.1177/1430.15819 · Cited by 27
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Jenkins, G., O'Byrne, K. J., Panizza, B. J., & Richard, D. J. (2013) · International Journal of Genomics · doi:10.1155/2013/464720 · Cited by 27
Holz, A., Paul, B., Zapf, A., Pantel, K., & Joosse, S. A. (2025) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2025.102999 · Cited by 26
TP53, PIK3CA, FBXW7 and KRAS Mutations in Esophageal Cancer Identified by Targeted Sequencing.
Zheng, H., Wang, Y., Tang, C., Jones, L. E., Ye, H., Zhang, G., Cao, W., Li, J., Liu, L., Liu, Z., et al. (2016) · PubMed · Cited by 26
Next-generation molecular diagnosis: single-cell sequencing from bench to bedside
Zhu, W., Zhang, X., Marjani, S. L., Zhang, J., Zhang, W., Wu, S., & Pan, X. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2368-x · Cited by 26
Sam, M. R., Tavakoli-Mehr, M., & Safaralizadeh, R. (2018) · Genes & Nutrition · doi:10.1186/s12263-018-0596-4 · Cited by 26
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Martins, M., Mansinho, A., Cruz-Duarte, R., Lobo-Martins, S., & Costa, L. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-02771-1_8 · Cited by 26
Capturing Tumor Heterogeneity and Clonal Evolution by Circulating Tumor DNA Profiling
Scherer, F. (2019) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-030-26439-0_11 · Cited by 26
Rossini, D., Germani, M. M., Pagani, F., Pellino, A., Dell’Aquila, E., Bensi, M., Liscia, N., Moretto, R., Boccaccino, A., Prisciandaro, M., et al. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2020.03.009 · Cited by 26
Afrin, S., Giampieri, F., Cianciosi, D., Álvarez-Suárez, J. M., Bullón, B., Amici, A., Quiles, J. L., Forbes-Hernández, T. Y., & Battino, M. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112484 · Cited by 26
Gong, R., Chen, M., Huang, C., Wong, H. L. X., Kwan, H. Y., & Bian, Z. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00834-2 · Cited by 26
Niu, C., Yang, J., Yan, K., Xie, J., Jiang, W., Li, B., & Wen, J. (2022) · iScience · doi:10.1016/j.isci.2022.104253 · Cited by 26
Genetic alterations shaping tumor response to anti-EGFR therapies
Vaquero, J., Pavy, A., Gonzalez‐Sanchez, E., Meredith, M., Arbelaiz, A., & Fouassier, L. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100863 · Cited by 26
Guha, M., Castellanos-Rizaldos, E., Liu, P., Mamon, H. J., & Makrigiorgos, G. M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1250 · Cited by 26
Future perspectives of circulating tumor DNA in colorectal cancer
Nadal, C., Winder, T. L., Gerger, A., & Tougeron, D. (2017) · Tumor Biology · doi:10.1177/1010428317705749 · Cited by 26
Urinary cell-free DNA as a prognostic marker for KRAS-positive advanced-stage NSCLC
Xie, F., Li, P., Gong, J., Tan, H., & Ma, J.-T. (2017) · Clinical & Translational Oncology · doi:10.1007/s12094-017-1754-7 · Cited by 26
Wang, X., Sheng, W., Wang, Y., Li, L., Li, Y., Zhang, S., Liu, X., Chen, S., & Zhen, Y. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00234 · Cited by 26
Goel, G. (2018) · Cancer Management and Research · doi:10.2147/cmar.s162967 · Cited by 26
Maurel, J., Alonso, V., Escudero, P., Fernández-Martos, C., Salud, A., Méndez, M., Gallego-Plazas, J., Rodríguez, J. R., Martín-Richard, M., Fernández-Plana, J., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00289 · Cited by 26
RasGRP1 is a potential biomarker for stratifying anti-EGFR therapy response in colorectal cancer
Gbenedio, O. M., Bonnans, C., Grün, D., Wang, C., Hatch, A. J., Mahoney, M. R., Barras, D., Matli, M. R., Miao, Y., García, K. C., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.127552 · Cited by 26
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Zmrzljak, U. P., Košir, R., Krivokapić, Z., Radojkovic, D. P., & Nikolić, A. (2021) · Genes · doi:10.3390/genes12020289 · Cited by 26
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Köstler, W. J., & Zielinski, C. C. (2014) · Springer eBooks · doi:10.1007/978-1-4939-2053-2_10 · Cited by 26
Li, Y., Xu, Z., Wang, S., Zhu, Y., Ma, D., Mu, Y., Ying, J., Li, J., & Xing, P. (2022) · Thoracic Cancer · doi:10.1111/1759-7714.14545 · Cited by 25
KRAS-related long noncoding RNAs in human cancers
Saliani, M., Mirzaiebadizi, A., Javadmanesh, A., Siavoshi, A., & Ahmadian, M. R. (2021) · Cancer Gene Therapy · doi:10.1038/s41417-021-00381-x · Cited by 25
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Bellio, C., Emperador, M., Castellano‐Escuder, P., Gris‐Oliver, A., Canals, F., Sánchez‐Pla, Á., Zamora, E., Arribas, J., Saura, C., Serra, V., et al. (2022) · Cancers · doi:10.3390/cancers14102562 · Cited by 25
Regorafenib in metastatic colorectal cancer
Bianchi, A. S., Zeppellini, A., Amatu, A., Ricotta, R., Bencardino, K. B., & Siena, S. (2014) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.2014.894887 · Cited by 25
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Self-citationPancreatic cancer genomics: insights and opportunities for clinical translation
Makohon-Moore, A. P., Brosnan‐Cashman, J. A., & Iacobuzio–Donahue, C. A. (2013) · Genome Medicine · doi:10.1186/gm430 · Cited by 25
Boysen, A. K., Wettergren, Y., Sørensen, B. S., Taflin, H. A., Gustavson, B., & Spindler, K. G. (2017) · Tumor Biology · doi:10.1177/1010428317730976 · Cited by 25
Rofi, E., Vivaldi, C., Re, M. D., Arrigoni, E., Crucitta, S., Funel, N., Fogli, S., Vasile, E., Musettini, G., Fornaro, L., et al. (2018) · Pharmacogenomics · doi:10.2217/pgs-2018-0149 · Cited by 25
Toward liquid biopsies in cancer treatment: application of circulating tumor DNA
Ahlborn, L. B., & Østrup, O. (2019) · Apmis · doi:10.1111/apm.12912 · Cited by 25
Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives
Moati, É., Taly, V., Garinet, S., Didelot, A., Taı̈eb, J., Laurent‐Puig, P., & Zaanan, A. (2021) · Cancers · doi:10.3390/cancers13194743 · Cited by 25
Ciracì, P., Germani, M. M., Pietrantonio, F., Manca, P., Lonardi, S., Busico, A., Bergamo, F., Burgio, V., Mannavola, F., Donato, S. D., et al. (2025) · Annals of Oncology · doi:10.1016/j.annonc.2025.10.002 · Cited by 24
Integrating anti-EGFR therapies in metastatic colorectal cancer.
Haraldsdóttir, S., & Bekaii‐Saab, T. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2078-6891.2013.028 · Cited by 24
Computational optimisation of targeted DNA sequencing for cancer detection
Martinez, P., McGranahan, N., Birkbak, N. J., Gerlinger, M., & Swanton, C. (2013) · Scientific Reports · doi:10.1038/srep03309 · Cited by 24
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Kline, C., & El‐Deiry, W. S. (2013) · Pharmaceuticals · doi:10.3390/ph6080988 · Cited by 24
Harlé, A., Filhine-Trésarrieu, P., Husson, M., Boidot, R., Rouyer, M., Dubois, C., Leroux, A., & Merlin, J. (2015) · Targeted Oncology · doi:10.1007/s11523-015-0404-7 · Cited by 24
Wang, Y., Liu, H., Hou, Y., Zhou, X., Liang, L., Zhang, Z., Shi, H., Xu, S., Hu, P., Zheng, Z., et al. (2018) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-018-2359-4 · Cited by 24
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Gawin, M., Kurczyk, A., Niemiec, J. A., Stanek‐Widera, A., Grela-Wojewoda, A., Adamczyk, A., Biskup-Frużyńska, M., Polańska, J., & Widłak, P. (2021) · Cancers · doi:10.3390/cancers13174349 · Cited by 24
Tsuji, A., Nakamura, M., Watanabe, T., Manaka, D., Matsuoka, H., Kataoka, M., Takeuchi, M., Ichikawa, W., & Fujii, M. (2021) · Targeted Oncology · doi:10.1007/s11523-021-00845-y · Cited by 24
Bestari, M. B., Joewono, I. R., & Syam, A. F. (2024) · Biomolecules · doi:10.3390/biom14030364 · Cited by 24
Han, H., Ma, J., Zhang, K., Li, W., Liu, C., ZHANG, Y., Zhang, G., Ma, P., WANG, L., Zhang, G., et al. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2663 · Cited by 24
Hickish, T., Cassidy, J., PROPPER, D. J., Chau, I., Falk, S. J., Ford, H. E. R., Iveson, T. J., Braun, M., Potter, V. A., Macpherson, I. R., et al. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.08.008 · Cited by 24
Picco, G., Petti, C., Sassi, F. P., Grillone, K., Migliardi, G., Rossi, T., Isella, C., Nicolantonio, F. D., Sarotto, I., Sapino, A., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw209 · Cited by 24
Self-citationBianchi, A. S., Siena, S., Tonini, G., Bardelli, A., & Santini, D. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.10.006 · Cited by 24
Self-citationFeedback activation of HER3 attenuates response to EGFR inhibitors in colon cancer cells
Bosch-Vilaró, A., Jacobs, B., Pomella, V., Asbagh, L. A., Kirkland, R. E., Michel, J., Singh, S., Liu, X., Kim, P., Weitsman, G. E., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13834 · Cited by 24
Targeting tumor cells with antibodies enhances anti-tumor immunity
Sun, Z., Fu, Y., & Peng, H. (2018) · Biophysics Reports · doi:10.1007/s41048-018-0070-2 · Cited by 24
Pastor, B., André, T., Henriques, J., Trouilloud, I., Tournigand, C., Jary, M., Mazard, T., Louvet, C., Azan, S., Bauer, A., et al. (2021) · Molecular Oncology · doi:10.1002/1878-0261.12972 · Cited by 24
Parsons, B. L., McKim, K. L., & Myers, M. B. (2017) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22110 · Cited by 24
Circulating Tumor DNA Analysis in Colorectal Cancer: From Dream to Reality
Antoniotti, C., Pietrantonio, F., Corallo, S., de Braud, F., Falcone, A., & Cremolini, C. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00397 · Cited by 24
Impact of tumor sequencing on the use of anticancer drugs
Thomas, F., Desmedt, C., Aftimos, P. G., & Awada, A. H. (2014) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000078 · Cited by 23
Panitumumab in Metastatic Colorectal Cancer: The Importance of Tumour RAS Status
Peeters, M., Karthaus, M., Rivera, F., Terwey, J.-H., & Douillard, J. (2015) · Drugs · doi:10.1007/s40265-015-0386-x · Cited by 23
Brijwani, N., Jain, M., Dhandapani, M., Zahed, F., Mukhopadhyay, P., Biswas, M., Khatri, D., Radhakrishna, V. D., Majumder, B., Radhakrishnan, P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01566-x · Cited by 23
Inhibition of Heat Shock Protein 90 as a Novel Platform for the Treatment of Cancer
Gao, C., Peng, Y., Wang, H., Fang, S., Zhang, M., Zhao, Q., & Liu, J. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190503145944 · Cited by 23
Choi, I. S., Kato, S., Fanta, P. T., Leichman, L., Okamura, R., Raymond, V. M., Lanman, R. B., Lippman, S. M., & Kurzrock, R. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0965 · Cited by 23
Induction of apoptosis increases sensitivity to detect cancer mutations in plasma
Marques, J. F., Junqueira-Neto, S., Pinheiro, J., Machado, J. C., & Costa, J. L. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2019.12.023 · Cited by 23
Banda, M., McKim, K. L., Myers, M. B., Inoue, M., & Parsons, B. L. (2020) · PLoS ONE · doi:10.1371/journal.pone.0238862 · Cited by 23
Use of Circulating Cell-Free DNA to Guide Precision Medicine in Patients with Colorectal Cancer
Morris, V. K., & Strickler, J. H. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-070119-120448 · Cited by 23
Direct Detection of Low Abundance Genes of Single Point Mutation
Mishra, S., Jeon, J., Kang, J., Song, S., Kim, T., Ban, C., Choi, H., Kim, Y., Kim, M., & Park, J. W. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c02728 · Cited by 23
He, J., & Wu, W. (2022) · Non-coding RNA Research · doi:10.1016/j.ncrna.2022.10.001 · Cited by 23
Challenges and Strategies to Combat Resistance Mechanisms in Thyroid Cancer Therapeutics
Gild, M. L., Bullock, M., Tsang, V., Clifton-Bligh, R. J., Robinson, B. G., & Wirth, L. J. (2023) · Thyroid · doi:10.1089/thy.2022.0704 · Cited by 24
Cherradi, S., Garambois, V., Marines, J., Andrade, A. F., Fauvre, A., Morand, O., Fargal, M., Mancouri, F., Ayrolles-Torro, A., Vié, N., et al. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01015-5 · Cited by 23
Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma
Mazurek, A. M., Fiszer-Kierzkowska, A., Rutkowski, T. W., Składowski, K., Pierzyna-Świtała, M., Ścieglińska, D., Woźniak, G., Głowacki, G., Kawczyński, R., & Małusecka, E. (2013) · Cancer Biomarkers · doi:10.3233/cbm-130371 · Cited by 23
Emerging treatment for advanced lung cancer withEGFRmutation
Inal, C., Yilmaz, E., Piperdi, B., Perez-Soler, R., & Cheng, H. (2015) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2015.1058778 · Cited by 23
Finding effective cancer therapies through loss of function genetic screens
Bernards, R. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.007 · Cited by 23
Chen, G., Yang, Z., Eshleman, J. R., Netto, G. J., & Lin, M. (2016) · BioMed Research International · doi:10.1155/2016/9850690 · Cited by 23
Ultrasensitive and high-efficiency screen of de novo low-frequency mutations by o2n-seq
Wang, K., Lai, S., Yang, X., Zhu, T., Lu, X., Wu, C., & Ruan, J. (2017) · Nature Communications · doi:10.1038/ncomms15335 · Cited by 23
Park, H.-J., Park, J.-B., Lee, S.-J., & Song, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081746 · Cited by 23
Monitoring resistance through liquid biopsy
Parikh, A. R., & Corcoran, R. B. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx650 · Cited by 23
Morgan, G., Mortensson, E., Legge, D., Gupta, B., Collard, T. J., Greenhough, A., & Williams, A. C. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.412 · Cited by 23
García‐Tojal, J., Gil‐García, R., Fouz, V. I., Madariaga, G., Lezama, L. M., Galletero, M. S., Borrás, J., Nollmann, F. I., Girón, C. G., Alcaraz, R., et al. (2017) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2017.12.005 · Cited by 23
Induction of N-Ras degradation by flunarizine-mediated autophagy
Zheng, Z.-Y., Li, J., Li, F., Zhu, Y., Cui, K., Wong, S. T. C., Chang, E. C., & Liao, Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-35237-2 · Cited by 23
Post, J. B., Hami, N., Mertens, A. E. E., Elfrink, S., Bos, J. L., & Snippert, H. J. G. (2019) · Oncotarget · doi:10.18632/oncotarget.26677 · Cited by 23
García-García, C., Rivas, M. A., Ibrahim, Y. H., Calvo, M. T., Gris‐Oliver, A., Rodríguez, O., Grueso, J., Antón, P., Guzmán, M., Aura, C. M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3091 · Cited by 23
Metadata
- Authors
- Misale, S., Yaeger, R., Hobor, S., Scala, E., Janakiraman, M., Liska, D., Valtorta, E., Schiavo, R., Buscarino, M., Siravegna, G., Bencardino, K., Cercek, A., Chen, C.-T., Veronese, S., Zanon, C., Sartore-Bianchi, A., Gambacorta, M., Gallicchio, M., Vakiani, E., Boscaro, V., Medico, E., Weiser, M., Siena, S., Di Nicolantonio, F., Solit, D., & Bardelli, A.
- Affiliations
- Candiolo Cancer Institute (IT)
- Memorial Sloan Kettering Cancer Center (US)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- University of Turin (IT)
- IFOM (IT)
- Corresponding author
- Solit, David
- Bardelli, Alberto
- ORCID
- Venue
- Nature
- Published
- 2012-06
- Volume
- 486
- Issue
- 7404
- Pages
- 532-536
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3927413
- OpenAlex
- W2062109911
- Cited by
- 1,889
- References
- 25
- Citations by year
- 2026: 75 · 2025: 73 · 2024: 81 · 2023: 115 · 2022: 129 · 2021: 138 · 2020: 134 · 2019: 163 · 2018: 161 · 2017: 171 · 2016: 177 · 2015: 163 · 2014: 145 · 2013: 133 · 2012: 28
- FWCI
- 73.66
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- European Commission (259015)
- Associazione Italiana per la Ricerca sul Cancro (5 x mille)
- Regione Piemonte
- National Cancer Institute (R01CA127240, P30CA008748, T32CA009207, R25CA020449)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- KRAS mutation, acquired drug resistance, anti-EGFR therapy, cetuximab resistance, colorectal cancer, EGFR, K-ras oncogene, circulating tumor DNA, tumor subclones, MEK inhibition, combination therapy, metastatic colorectal cancer, tumor heterogeneity
- MeSH terms
- Cetuximab, Panitumumab, Alleles, Antibodies, Monoclonal, Humans, Mutation, Promoter Regions, Genetic, Proto-Oncogene Proteins, Genes, ras, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), Disease Progression, ras Proteins, Drug Resistance, Neoplasm, Mitogen-Activated Protein Kinase Kinases, Cell Line, Tumor, Antibodies, Monoclonal, Humanized, ErbB Receptors
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