The DOI matches its Crossref record; 23 of the 25 references it cites were found in a registry or an index.
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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
“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]
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
“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
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
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
Cited by
Sorted by citations
Items 501–600 of 1,014
Maia, M. C., Bergerot, P. G., Dizman, N., Hsu, J., Jones, J. O., Lanman, R. B., Banks, K. C., & Pal, S. K. (2017) · Kidney Cancer · doi:10.3233/kca-170007 · Cited by 57
Wang, A., Li, Y., Zhao, Q., & Fan, L. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8857 · Cited by 57
KRAS: A Druggable Target in Colon Cancer Patients
Negri, F., Bottarelli, L., de’Angelis, G. L., & Gnetti, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084120 · Cited by 57
Aung, K. L., Donald, E. L., Ellison, G., Bujac, S. R., Fletcher, L. M., Cantarini, M., Brady, G., Orr, M. C. M., Clack, G., Ranson, M., et al. (2014) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2013.12.004 · Cited by 56
Rubinson, D. A., Höchster, H. S., Ryan, D. P., Wolpin, B. M., McCleary, N. J., Abrams, T. A., Chan, J. A.-W., Iqbal, S., Lenz, H. J., Lim, D. W., et al. (2013) · Investigational New Drugs · doi:10.1007/s10637-013-9956-5 · Cited by 56
Mechanisms of intrinsic and acquired resistance to kinase‐targeted therapies
Bagrodia, S., Smeal, T., & Abraham, R. T. (2012) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12007 · Cited by 56
CD133+ liver cancer stem cells resist interferon-gamma-induced autophagy
Li, J., Chen, J.-N., Zeng, T., He, F., Chen, S.-P., Ma, S., Bi, J., Zhu, X., & Guan, X. (2016) · BMC Cancer · doi:10.1186/s12885-016-2050-6 · Cited by 56
Bianchi, A. S., Loupakis, F., Argilés, G., & Prager, G. W. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw191 · Cited by 56
BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells
He, K., Chen, D., Ruan, H., Li, X., Tong, J., Xu, X. M., Zhang, L., & Yu, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10277 · Cited by 56
Fujii, T., Barzi, A., Bianchi, A. S., Cassingena, A., Siravegna, G., Karp, D. D., Piha-Paul, S. A., Subbiah, V., Tsimberidou, A. M., Huang, H. J., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2592 · Cited by 56
Self-citationMcEvoy, A. C., Calapre, L., Pereira, M. R., Giardina, T. M., Robinson, C., Khattak, M. A., Meniawy, T. M., Pritchard, A. L., Hayward, N. K., Amanuel, B., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20354 · Cited by 56
Huang, L. J., Wen, C., Yang, X., Lou, Q., Wang, X., Che, J., Chen, J., Yang, Z., Wu, X., Huang, M., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0320-8 · Cited by 56
WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation
Jeong, W.-J., Park, J., Kim, W.-S., Ro, E. J., Jeon, S. H., Lee, S., Park, Y. N., Min, D. S., & Choi, K. (2019) · Nature Communications · doi:10.1038/s41467-018-08230-6 · Cited by 56
Jacob, S. L., Davis, A. A., Gerratana, L., Velimirovic, M., Shah, A. N., Wehbe, F., Katam, N., Zhang, Q., Flaum, L., Siziopikou, K. P., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1566 · Cited by 56
Duffy, M. J., & Crown, J. P. (2022) · Clinical Chemistry · doi:10.1093/clinchem/hvac121 · Cited by 55
Linking Tumor Mutations to Drug Responses via a Quantitative Chemical–Genetic Interaction Map
Martins, M. M., Zhou, A. Y., Corella, A. N., Horiuchi, D., Yau, C. S. F., Rakhshandehroo, T., Gordan, J. D., Levin, R. S., Johnson, J. R., Jascur, J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0552 · Cited by 55
Cappuzzo, F., Sacconi, A., Landi, L. M., Ludovini, V., Biagioni, F., D’Incecco, A., Capodanno, A., Salvini, J., Corgna, E., Cupini, S., et al. (2013) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2013.11.006 · Cited by 55
Gao, Y., Song, P., Li, H., Jia, H. M., & Zhang, B. (2017) · BMC Cancer · doi:10.1186/s12885-017-3474-3 · Cited by 55
Mansukhani, S., Barber, L. J., Kleftogiannis, D., Moorcraft, S. Y., Davidson, M., Woolston, A., Proszek, P., Griffiths, B. L., Fenwick, K., Herman, B., et al. (2018) · Clinical Chemistry · doi:10.1373/clinchem.2018.289629 · Cited by 55
Jiang, P., Lee, W., Li, X., Johnson, C., Liu, J. S., Brown, M. A., Aster, J. C., & Liu, X. S. (2018) · Cell Systems · doi:10.1016/j.cels.2018.01.009 · Cited by 55
Yonesaka, K. (2021) · Cancers · doi:10.3390/cancers13051047 · Cited by 55
Tan, L., Tran, B., Tie, J., Markman, B., Ananda, S., Tebbutt, N. C., Michael, M., Link, E. K., Wong, S. Q., Chandrashekar, S., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-3094 · Cited by 54
Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
Seow, H. F., Yip, W. K., & Fifis, T. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s95101 · Cited by 54
Re-Evaluating Clonal Dominance in Cancer Evolution
Burrell, R. A., & Swanton, C. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.04.002 · Cited by 54
Colorectal Cancer in the Arab World - Screening Practices and Future Prospects
Arafa, M. A., & Farhat, K. H. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.17.7425 · Cited by 54
A population genetics perspective on the determinants of intra-tumor heterogeneity
Hu, Z., Sun, R., & Curtis, C. N. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.03.001 · Cited by 54
Precision treatment in colorectal cancer: Now and the future
Yau, T. O. (2019) · JGH Open · doi:10.1002/jgh3.12153 · Cited by 54
Profiling DNA mutation patterns by SERS fingerprinting for supervised cancer classification
Wu, L., Teixeira, A., Garrido‐Maestu, A., Muinelo‐Romay, L., Lima, L., Santos, L. L., Prado, M., & Diéguez, L. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112392 · Cited by 54
Sunakawa, Y., Nakamura, M., Ishizaki, M., Kataoka, M., Satake, H., Kitazono, M., Yanagisawa, H., Kawamoto, Y., Kuramochi, H., Ohori, H., et al. (2020) · JCO Precision Oncology · doi:10.1200/po.20.00109 · Cited by 54
Esposito, C., Rachiglio, A. M., La Porta, M. L., Sacco, A., Roma, C., Iannaccone, A., Tatangelo, F., Forgione, L., Pasquale, R., Barbaro, A., et al. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.26340 · Cited by 53
Troiani, T., Zappavigna, S., Martinelli, E., Addeo, S. R., Stiuso, P., Ciardiello, F., & Caraglia, M. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2012.756469 · Cited by 53
SUN, W., Sun, Y., Zhu, M., Wang, Z., Zhang, H., Xin, Y., Jiang, G., Guo, X., Zhang, Z., & Liu, Y. (2013) · Oncology Reports · doi:10.3892/or.2013.2949 · Cited by 53
Patient monitoring through liquid biopsies using circulating tumor DNA
Ulz, P., Heitzer, E., Geigl, J. B., & Speicher, M. R. (2017) · International Journal of Cancer · doi:10.1002/ijc.30759 · Cited by 53
Liquid Biopsy in Tumor Genetic Diagnosis
Jung, A., & Kirchner, T. (2018) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2018.0169 · Cited by 53
Circulating tumor cells in clinical research and monitoring patients with colorectal cancer
Burz, C. C., Pop, V.-V., Buiga, R., Sur, D. G., Samaşcă, G., Aldea, C. O., & Lupan, I. (2018) · Oncotarget · doi:10.18632/oncotarget.25337 · Cited by 53
The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer
Hon, K. W., Abidin, S. A. Z., Othman, I., & Naidu, R. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.768861 · Cited by 53
Kato, S., Schwaederlé, M. C., Fanta, P. T., Okamura, R., Leichman, L., Lippman, S. M., Lanman, R. B., Raymond, V. M., Talasaz, A., & Kurzrock, R. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00158 · Cited by 52
Wang, C. Y., Guo, S., Wang, J. Y., Liu, F., Zhang, Y. Y., Yari, H., Yan, X. G., Jin, L., Zhang, X. D., & Jiang, C. C. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0778 · Cited by 52
Liu, X., George, G. C., Tsimberidou, A. M., Naing, A., Wheler, J. J., Kopetz, S., Fu, S., Piha-Paul, S. A., Eng, C., Falchook, G. S., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1701-3 · Cited by 52
Jankú, F., Zhang, S., Waters, J., Liu, L., Huang, H. J., Subbiah, V., Hong, D. S., Karp, D. D., Fu, S., Cai, X., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0291 · Cited by 52
The importance of Ras in drug resistance in cancer
Healy, F. M., Prior, I. A., & MacEwan, D. J. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15420 · Cited by 52
Spindler, K. G., Pallisgaard, N., Appelt, A. L., Andersen, R. F., Schou, J. V., Nielsen, D. L., Pfeiffer, P., Yilmaz, M., Johansen, J. S., Høgdall, E. V. S., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.06.118 · Cited by 51
Genetics of Hepatocellular Carcinoma: From Tumor to Circulating DNA
Campani, C., Zucman‐Rossi, J., & Nault, J. (2023) · Cancers · doi:10.3390/cancers15030817 · Cited by 52
Tarabichi, M., Antoniou, A., Saiselet, M., Pita, J. M. G., Andry, G., Dumont, J. E., Detours, V., & Maenhaut, C. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9431-y · Cited by 51
High Intra- and Inter-Tumoral Heterogeneity of RAS Mutations in Colorectal Cancer
Jeantet, M., Tougeron, D., Tachon, G., Cortes, U., Archambaut, C., Fromont, G., & Karayan, L. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122015 · Cited by 51
Liquid Biopsies for Monitoring Temporal Genomic Heterogeneity in Breast and Colon Cancers
Venesio, T., Siravegna, G., Bardelli, A., & Sapino, A. (2017) · Pathobiology · doi:10.1159/000473882 · Cited by 51
Self-citationGoldberg, R. M., Montagut, C. O., Wainberg, Z. A., Ronga, P., Audhuy, F., Taı̈eb, J., Stintzing, S., Siena, S., & Santini, D. (2018) · ESMO Open · doi:10.1136/esmoopen-2018-000353 · Cited by 51
Self-citationAmplification-free SERS analysis of DNA mutation in cancer cells with single-base sensitivity
Wu, L., Garrido‐Maestu, A., Guerreiro, J. R. L., Carvalho, S., Abalde‐Cela, S., Prado, M., & Diéguez, L. (2019) · Nanoscale · doi:10.1039/c9nr00501c · Cited by 51
Clinical Perspective and Translational Oncology of Liquid Biopsy
Fernández‐Lázaro, D., Garcı́a, J. L., Caballero-García, A., del Castillo, A. C., Hueso, M. V., & Cruz, J. J. (2020) · Diagnostics · doi:10.3390/diagnostics10070443 · Cited by 50
Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
Pal, S., Sharma, A. K., Mathew, S. P., & Jaganathan, B. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.955476 · Cited by 50
Nucleotide resolution analysis of TMPRSS2 and ERG rearrangements in prostate cancer
Weier, C. A., Haffner, M. C., Mosbruger, T. L., Esopi, D., Hicks, J. L., Zheng, Q., Fedor, H. L., Isaacs, W. B., Marzo, A. M. D., Nelson, W. G., et al. (2013) · The Journal of Pathology · doi:10.1002/path.4186 · Cited by 50
Opportunities and challenges provided by crosstalk between signalling pathways in cancer
Prahallad, A., & Bernards, R. (2015) · Oncogene · doi:10.1038/onc.2015.151 · Cited by 50
Qian, Y., Xia, S., & Feng, Z. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.12.119 · Cited by 50
Liquid biopsy: unlocking the potentials of cell-free DNA
Chu, D. T. W., & Park, B. H. (2017) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-017-2137-8 · Cited by 50
Połom, K., Das, K., Marrelli, D., Roviello, G., Pascale, V., Voglino, C., Rho, H., Tan, P. B. O., & Roviello, F. (2017) · Pathology & Oncology Research · doi:10.1007/s12253-017-0348-6 · Cited by 50
Graziani, V., Scognamiglio, M., Belli, V., Esposito, A., D’Abrosca, B., Chambery, A., Russo, R., Panella, M., Russo, A., Ciardiello, F., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-23704-9 · Cited by 50
Preclinical models for precision oncology
Ibarrola‐Villava, M., Cervantes, A. M. R., & Bardelli, A. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.004 · Cited by 50
Self-citationRas Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target
Chen, M., Peters, A., Huang, T., & Nan, X. (2015) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557515666151001152212 · Cited by 49
Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer
Graham, D. M., Coyle, V. M., Kennedy, R. D., & Wilson, R. H. (2016) · Current Colorectal Cancer Reports · doi:10.1007/s11888-016-0312-y · Cited by 49
Overcoming treatment resistance in cancer: Current understanding and tactics
Wu, G. J., Wilson, G., George, J., Liddle, C., Hebbard, L., & Qiao, L. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.04.018 · Cited by 49
Papadopoulos, N. (2019) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-030-26439-0_9 · Cited by 49
The Multifaceted Role of miR-21 in Pancreatic Cancers
Chen, C., Demirkhanyan, L. H., & Gondi, C. S. (2024) · Cells · doi:10.3390/cells13110948 · Cited by 49
Self-citationCirculating Free DNA in a Screening Program for Early Colorectal Cancer Detection
Perrone, F., Lampis, A., Bertan, C. M., Verderio, P., Ciniselli, C. M., Pizzamiglio, S., Frattini, M., Nucifora, M., Molinari, F., Gallino, G., et al. (2014) · Tumori Journal · doi:10.1177/030089161410000201 · Cited by 48
Saki, M. R., Toulany, M., & Rodemann, H. P. (2013) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2013.06.023 · Cited by 48
Realizing the Potential of Plasma Genotyping in an Age of Genotype-Directed Therapies
Luke, J. J., Oxnard, G. R., Paweletz, C. P., Camidge, D. R., Heymach, J. V., Solit, D. B., Johnson, B. E., & for the Cell Free DNA Working Group (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju214 · Cited by 48
Self-citationLahti, S. J., Xing, M., Zhang, D., Lee, J. J., Magnetta, M. J., & Kim, H. S. (2015) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2015.05.032 · Cited by 48
Jankú, F., Huang, H. J., Fujii, T., Shelton, D. N., Madwani, K., Fu, S., Tsimberidou, A. M., Piha-Paul, S. A., Wheler, J. J., Zinner, R., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw670 · Cited by 48
Berger, A. W., Schwerdel, D., Welz, H., Marienfeld, R. B., Schmidt, S. A., Kleger, A., Ettrich, T. J., & Seufferlein, T. T. W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174308 · Cited by 48
Selective targeting of point-mutated KRAS through artificial microRNAs
Acunzo, M., Romano, G., Nigita, G., Veneziano, D., Fattore, L., Laganà, A., Zanesi, N., Fadda, P., Fassan, M., Rizzotto, L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620562114 · Cited by 48
A Prognostic Model for Colon Cancer Patients Based on Eight Signature Autophagy Genes
Xu, J., Dai, S., Yuan, Y., Xiao, Q., & Ding, K. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602174 · Cited by 48
Jung, S.-A., Lee, D.-H., Moon, J.-H., Hong, S.-W., Shin, J.-S., Hwang, I. Y., Shin, Y. J., Kim, J. H., Gong, E.-Y., Kim, S.-M., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.009 · Cited by 47
Erve, I. V. ’., Medina, J. E., Leal, A., Papp, E., Phallen, J. A., Adleff, V., Chiao, E. J., Arun, A. S., Bolhuis, K., Simmons, J. K., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-2538 · Cited by 47
Raimondi, C., Nicolazzo, C., Gradilone, A., Giannini, G., FALCO, E. D., Chimenti, I., Varriale, E., Hauch, S., Plappert, L., Cortesi, E., et al. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.28020 · Cited by 47
Adapting conventional cancer treatment for immunotherapy
Qiao, J., Liu, Z., & Fu, Y. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1393-4 · Cited by 47
Circulating cell-free nucleic acids as biomarkers in colorectal cancer screening and diagnosis
Tóth, K., Barták, B. K., Tulassay, Z., & Molnar, B. A. (2015) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2016.1132164 · Cited by 47
Onstenk, W., Sieuwerts, A. M., Mostert, B., Lalmahomed, Z. S., Vries, J. B., van Galen, A., Smid, M., Kraan, J., Van, M. N., de Weerd, V., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10175 · Cited by 47
Cell-Free DNA in Oncology: Gearing up for Clinic
Ulrich, B. C., & Paweletz, C. P. (2017) · Annals of Laboratory Medicine · doi:10.3343/alm.2018.38.1.1 · Cited by 47
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
Vivancos, A. P., Aranda, E., Benavides, M., Élez, E., Gómez‐España, M. A., Toledano‐Fonseca, M., Álvarez, M., Chica-Parrado, M. D. R., García‐Barberán, V., & Díaz‐Rubio, E. (2019) · Scientific Reports · doi:10.1038/s41598-019-45616-y · Cited by 47
Joosten, S. P. J., Spaargaren, M., Clevers, H. C., & Pals, S. T. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188437 · Cited by 47
USP19 exacerbates lipogenesis and colorectal carcinogenesis by stabilizing ME1
Zhu, Y., Gu, L., Lin, X., Zhou, X., Lu, B., Liu, C., Lei, C., Zhou, F., Zhao, Q., Prochownik, E. V., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110174 · Cited by 47
Kalikaki, A., Politaki, H., Souglakos, J., Apostolaki, S., Papadimitraki, E., Georgoulia, N., Tzardi, M. N., Mavroudis, D., Georgoulias, V., & Voutsina, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104902 · Cited by 46
Rowland, A., Dias, M. M., Wiese, M. D., Kichenadasse, G., McKinnon, R. A., Karapetis, C. S., & Sorich, M. J. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.025 · Cited by 46
Screening for circulating RAS/RAF mutations by multiplex digital PCR
Andersen, R. F., & Jakobsen, A. K. M. (2016) · Clinica Chimica Acta · doi:10.1016/j.cca.2016.05.007 · Cited by 46
Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease
Yarden, Y., & Wheeler, D. L. (2014) · Springer eBooks · doi:10.1007/978-1-4939-2053-2 · Cited by 44
Extending Circulating Tumor DNA Analysis to Ultralow Abundance Mutations: Techniques and Challenges
Rodda, A. E., Parker, B. J., Spencer, A. G., & Corrie, S. R. (2018) · ACS Sensors · doi:10.1021/acssensors.7b00953 · Cited by 46
Furuki, H., Yamada, T., Takahashi, G., Iwai, T., Koizumi, M., Shinji, S., Yokoyama, Y., Takeda, K., Taniai, N., & Uchida, E. (2018) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2018.01.224 · Cited by 46
Pirazzoli, V., Ayeni, D. O., Meador, C. B., Sanganahalli, B. G., Hyder, F., de Stanchina, E., Goldberg, S. B., Pao, W. J., & Politi, K. A. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0620 · Cited by 46
Advanced Treatment for Basal Cell CarcinomasPreprint
Atwood, S. X., Whitson, R. J., & Oro, A. E. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a013581 · Cited by 46
Xu, J., Wang, P., Yang, H. J., Zhou, J., Li, Y., Li, X., Xue, W., Yu, C., Tian, Y., & Zhu, F. (2016) · BioMed Research International · doi:10.1155/2016/2509385 · Cited by 45
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
Mengoli, M. C., Barbieri, F., Bertolini, F., Tiseo, M., & Rossi, G. (2016) · Lung Cancer · doi:10.1016/j.lungcan.2016.01.002 · Cited by 47
Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance
Ali, M., Kaltenbrun, E., Anderson, G. R., Stephens, S. J., Arena, S., Bardelli, A., Counter, C. M., & Wood, K. C. (2017) · Nature Communications · doi:10.1038/ncomms15617 · Cited by 45
Self-citationYao, Y.-M., Donoho, G. P., Iversen, P. W., Zhang, Y., Horn, R. D. V., Forest, A., Novosiadly, R. D., Webster, Y., Ebert, P. J., Bray, S. M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3250 · Cited by 45
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
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-citationEntrectinib resistance mechanisms in ROS1-rearranged non-small cell lung cancer
Ku, B. M., Bae, Y. H., Lee, K. Y., Sun, J., Lee, S., Ahn, J. S., Park, K., & Ahn, M. (2019) · Investigational New Drugs · doi:10.1007/s10637-019-00795-3 · Cited by 45
Qawoogha, S. S., & Shahiwala, A. (2020) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2020.1715431 · Cited by 45
Chibuk, J., Flory, A., Kruglyak, K. M., Leibman, N. F., Nahama, A., Dharajiya, N. G., van den Boom, D., Jensen, T. J., Friedman, J. S., Shen, M. R., et al. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.664718 · Cited by 45
Genetic Alterations of Metastatic Colorectal Cancer
Testa, U., Castelli, G., & Pelosi, E. (2020) · Biomedicines · doi:10.3390/biomedicines8100414 · Cited by 44
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
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
