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 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
“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
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
Flagged first, then by citations
2 of the 25 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–200 of 1,014
Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer
Strickler, J. H., Loree, J. M., Ahronian, L. G., Parikh, A. R., Niedzwiecki, D., Pereira, A. A. L., McKinney, M. S., Korn, W. M., Atreya, C. E., Banks, K. C., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1009 · Cited by 300
Immunotherapy, Inflammation and Colorectal Cancer
Lichtenstern, C. R., Ngu, R. K., Shalapour, S., & Karin, M. (2020) · Cells · doi:10.3390/cells9030618 · Cited by 296
Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer
Aubert, L., Nandagopal, N., Steinhart, Z., Lavoie, G., Nourreddine, S., Berman, J. M., Saba-El-Leil, M. K., Papadopoli, D. J., Lin, S., Hart, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17549-y · Cited by 300
Mao, M., Tian, F., Mariadason, J. M., Tsao, C. C., Lemos, R., Dayyani, F., Gopal, Y. N. V., Jiang, Z.-Q., Wistuba, I. I., Tang, X. M., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1446 · Cited by 290
Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living
Heitzer, E., Auinger, L., & Speicher, M. R. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.01.012 · Cited by 290
Emerging concepts in liquid biopsies
Perakis, S. O., & Speicher, M. R. (2017) · BMC Medicine · doi:10.1186/s12916-017-0840-6 · Cited by 288
Bianchi, A. S., Pietrantonio, F., Lonardi, S., Mussolin, B., Rua, F., Crisafulli, G., Bartolini, A., Fenocchio, E., Amatu, A., Manca, P., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01886-0 · Cited by 287
Self-citationCancer heterogeneity—a multifaceted view
Melo, F. D. S. E., Vermeulen, L., Fessler, E., & Medema, J. P. (2013) · EMBO Reports · doi:10.1038/embor.2013.92 · Cited by 287
Mutational signatures: emerging concepts, caveats and clinical applications
Koh, C. C., Degasperi, A., Zou, X., Momen, S., & Nik‐Zainal, S. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00377-7 · Cited by 291
Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection
Fiala, C., & Diamandis, E. P. (2018) · BMC Medicine · doi:10.1186/s12916-018-1157-9 · Cited by 284
Antitumour immunity regulated by aberrant ERBB family signalling
Kumagai, S., Koyama, S., & Nishikawa, H. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-020-00322-0 · Cited by 288
Oncogenic mutations in cervical cancer
Wright, A. A., Howitt, B. E., Myers, A. P., Dahlberg, S. E., Palescandolo, E., Hummelen, P. V., MacConaill, L. E., Shoni, M., Wagle, N., Jones, R. T., et al. (2013) · Cancer · doi:10.1002/cncr.28288 · Cited by 280
MALT1 Small Molecule Inhibitors Specifically Suppress ABC-DLBCL In Vitro and In Vivo
Fontán, L., Yang, C., Kabaleeswaran, V., Volpon, L., Osborne, M. J., Beltrán, E., García, M. A. M., Cerchietti, L. C. A., Shaknovich, R., Yang, S. N., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.11.003 · Cited by 274
Targeting the Tumor Microenvironment with Interferon-β Bridges Innate and Adaptive Immune Responses
Yang, X., Zhang, X., Fu, M. L., Weichselbaum, R. R., Gajewski, T. F., Guo, Y., & Fu, Y. (2014) · Cancer Cell · doi:10.1016/j.ccr.2013.12.004 · Cited by 274
Zhou, H., Zhu, L., Song, J. H., Wang, G., Li, P., Li, W., Luo, P., Sun, X., Wu, J., Liu, Y., et al. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01556-2 · Cited by 273
Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer
Arena, S., Bellosillo, B., Siravegna, G., Martínez, A., Cañadas, I., Lazzari, L., Ferruz, N., Russo, M., Misale, S., González, I., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2821 · Cited by 271
Self-citationCancer evolution: Darwin and beyond
Vendramin, R., Litchfield, K., & Swanton, C. (2021) · The EMBO Journal · doi:10.15252/embj.2021108389 · Cited by 269
Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples
Russano, M., Napolitano, A., Ribelli, G., Iuliani, M., Simonetti, S., Citarella, F., Pantano, F., Dell’Aquila, E., Anesi, C., Silvestris, N., et al. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01601-2 · Cited by 267
Misale, S., Arena, S., Lamba, S., Siravegna, G., Lallo, A., Hobor, S., Russo, M., Buscarino, M., Lazzari, L., Sartore-Bianchi, A., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007947 · Cited by 263
Self-citationHeterogeneity in Colorectal Cancer: A Challenge for Personalized Medicine?
Molinari, C., Marisi, G., Passardi, A., Matteucci, L., De Maio, G., & Ulivi, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123733 · Cited by 262
Yu, H. A., Suzawa, K., Jordan, E., Zehir, A., Ni, A., Kim, R., Kris, M. G., Hellmann, M. D., Li, B. T., Somwar, R., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2961 · Cited by 259
Self-citationA Convergence-Based Framework for Cancer Drug Resistance
Konieczkowski, D. J., Johannessen, C. M., & Garraway, L. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.025 · Cited by 258
Morelli, M. P., Overman, M. J., Dasari, A. N., Kazmi, S. M. A., Mazard, T., Vilar, E., Morris, V. K., Lee, M. S., Herron, D. S., Eng, C., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv005 · Cited by 256
Kortüm, K. M., Mai, E. K., Hanafiah, N. H., Shi, C.-X., Zhu, Y.-X., Bruins, L., Barrio, S., Jedlowski, P., Merz, M., Xu, J., et al. (2016) · Blood · doi:10.1182/blood-2016-02-698092 · Cited by 255
Woolston, A., Khan, K., Spain, G., Barber, L. J., Griffiths, B., Gonzalez-Exposito, R., Hornsteiner, L., Punta, M., Patil, Y., Newey, A., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.05.013 · Cited by 254
S3-Leitlinie – Kolorektales Karzinom
Schmiegel, W., Buchberger, B., Follmann, M., Graeven, U., Heinemann, V., Langer, T. G., Nothacker, M., Porschen, R., Rödel, C. M., Rösch, T., et al. (2017) · Zeitschrift für Gastroenterologie · doi:10.1055/s-0043-121106 · Cited by 247
The Role of EREG/EGFR Pathway in Tumor Progression
Cheng, W., Feng, P., Lee, K., Chen, K.-Y., Sun, W.-L., Hiệp, N. V., Luo, C.-S., & Wu, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312828 · Cited by 246
Circulating Tumor DNA as Biomarkers for Cancer Detection
Han, X., Wang, J., & Sun, Y. (2017) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.12.004 · Cited by 246
The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients
Elshimali, Y., Khaddour, H., Sarkissyan, M., Wu, Y., & Vadgama, J. V. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140918925 · Cited by 242
Precision oncology in metastatic colorectal cancer — from biology to medicine
Nicolantonio, F. D., Vitiello, P. P., Marsoni, S., Siena, S., Tabernero, J. M., Trusolino, L., Bernards, R., & Bardelli, A. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00495-z · Cited by 244
Self-citationCirculating tumor DNA: current challenges for clinical utility
Dang, D. K., & Park, B. H. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154941 · Cited by 239
Immune Escape and Survival Mechanisms in Circulating Tumor Cells of Colorectal Cancer
Steinert, G., Schölch, S., Niemietz, T., Iwata, N., García, S. A., Behrens, B., Voigt, A. Y., Kloor, M., Benner, A., Bork, U., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-1885 · Cited by 236
Mouliere, F. C., Messaoudi, S. E., Pang, D., Dritschilo, A., & Thierry, A. R. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.02.005 · Cited by 234
The influence of subclonal resistance mutations on targeted cancer therapy
Schmitt, M. W., Loeb, L. A., & Salk, J. J. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.175 · Cited by 234
Targeting tumour-supportive cellular machineries in anticancer drug development
Dobbelstein, M., & Moll, U. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4201 · Cited by 233
Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Zhu, C., Guan, X., Zhang, X., Luan, X., Song, Z., Cheng, X., Zhang, W., & Qin, J.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01629-2 · Cited by 231
Overview on Clinical Relevance of Intra-Tumor Heterogeneity
Stanta, G., & Bonin, S. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00085 · Cited by 227
Khan, K. H., Cunningham, D., Werner, B., Vlachogiannis, G., Spiteri, I., Heide, T., Fernández-Mateos, J., Vatsiou, A. I., Lampis, A., Darvish-Damavandi, M., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0891 · Cited by 227
Shu, Y., Wu, X., Tong, X., Wang, X., Chang, Z., Mao, Y., Chen, X., Sun, J., Wang, Z., Hong, Z., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-00520-1 · Cited by 226
Martinelli, E., Ciardiello, D., Martini, G., Troiani, T., Cardone, C., Vitiello, P. P., Normanno, N., Rachiglio, A. M., Maiello, E., Latiano, T., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2019.10.007 · Cited by 225
Guidance for laboratories performing molecular pathology for cancer patients
Cree, I. A., Deans, Z. C., Ligtenberg, M. J. L., Normanno, N., Edsjö, A., Rouleau, É., Solé, F. G., Thunnissen, E., Timens, W., Schuuring, E. M. D., et al. (2014) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2014-202404 · Cited by 223
Drug resistance to targeted therapies: Déjà vu all over again
Groenendijk, F. H., & Bernards, R. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.05.004 · Cited by 222
Resistance to TRK inhibition mediated by convergent MAPK pathway activation
Cocco, E., Schram, A. M., Kulick, A. R., Misale, S., Won, H. H., Yaeger, R. D., Razavi, P., Ptashkin, R. N., Hechtman, J. F., Toska, E., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0542-z · Cited by 222
Self-citationPI3K and MEK inhibitor combinations: examining the evidence in selected tumor types
Britten, C. D. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2121-1 · Cited by 215
Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer
Van Emburgh, B. O., Arena, S., Siravegna, G., Lazzari, L., Crisafulli, G., Corti, G., Mussolin, B., Baldi, F., Buscarino, M., Bartolini, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms13665 · Cited by 214
Self-citationCancer drug-tolerant persister cells: from biological questions to clinical opportunities
Russo, M., Chen, M., Mariella, E., Peng, H., Rehman, S. K., Sancho, E., Sogari, A., Toh, T. S., Balaban, N. Q., Batlle, E., et al. (2024) · Nature Reviews Cancer · doi:10.1038/s41568-024-00737-z · Cited by 210
Self-citationThe Latest Battles Between EGFR Monoclonal Antibodies and Resistant Tumor Cells
Cai, W.-Q., Zeng, L.-S., Wang, L., Wang, Y., Cheng, J.-T., Zhang, Y., Han, Z.-W., Zhou, Y., Huang, S.-L., Wang, X.-W., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01249 · Cited by 208
Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy
Lee, J., Liu, Z., Sa, J. K., Shin, S. H., Wang, J., Bordyuh, M., Cho, H. J., Elliott, O., Chu, T., Choi, S. W., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0209-6 · Cited by 207
Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors
García‐Foncillas, J., Sunakawa, Y., Aderka, D., Wainberg, Z. A., Ronga, P., Witzler, P., & Stintzing, S. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00849 · Cited by 207
A Decision Support Framework for Genomically Informed Investigational Cancer Therapy
Meric‐Bernstam, F., Johnson, A. M., Holla, V. R., Bailey, A. M., Brusco, L., Chen, K., Routbort, M. J., Patel, K. P., Zeng, J., Kopetz, S., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv098 · Cited by 202
Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions
Cheng, M. L., Pectasides, E., Hanna, G. J., Parsons, H. A., Choudhury, A. D., & Oxnard, G. R. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21650 · Cited by 201
Harouaka, R. A., Kang, Z., Zheng, S.-Y., & Cao, L. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.004 · Cited by 200
EGFR-TKI resistance in NSCLC patients: mechanisms and strategies.
Lin, Y., Wang, X., & Jin, H. (2014) · Europe PMC (PubMed Central) · Cited by 198
Tissue-Specific Oncogenic Activity of KRASA146T
Poulin, E. J., Bera, A. K., Lu, J., Lin, Y.-J., Strasser, S. D., Paulo, J. A., Huang, T. Q., Morales, C., Yan, W., Cook, J., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1220 · Cited by 197
Tumor Evolution as a Therapeutic Target
Amirouchene-Angelozzi, N., Swanton, C., & Bardelli, A. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0343 · Cited by 197
Self-citationPrecision Oncology: The Road Ahead
Senft, D., Leiserson, M. D. M., Ruppin, E., & Ronai, Z. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.003 · Cited by 199
Oncogenic Kras drives invasion and maintains metastases in colorectal cancer
Boutin, A. T., Liao, W.-T., Wang, M., Hwang, S. S., Karpinets, T. V., Cheung, H., Chu, G. C., Jiang, S., Hu, J., Chang, K., et al. (2017) · Genes & Development · doi:10.1101/gad.293449.116 · Cited by 195
Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
Gu, Y., Yang, R., Zhang, Y., Guo, M., Takehiro, K., Zhan, M., Yang, L., & Wang, H. (2025) · Molecular Biomedicine · doi:10.1186/s43556-024-00239-2 · Cited by 184
Grasselli, J., Élez, E., Caratù, G., Matito, J., Santos, C., Macarulla, T. M., Vidal, J., García, M. D. S., Viéitez, J. M., Páez, D., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx112 · Cited by 188
Frenel, J., Carreira, S., GOODALL, J. C., Roda, D., Pérez-López, R., Tunariu, N., Riisnaes, R., Miranda, S., Figueiredo, I., Rodrigues, D. N., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0584 · Cited by 186
Evolution and dynamics of pancreatic cancer progression
Yachida, S., & Iacobuzio–Donahue, C. A. (2013) · Oncogene · doi:10.1038/onc.2013.29 · Cited by 185
ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients
Chu, D. T. W., Paoletti, C., Gersch, C. L., VanDenBerg, D. A., Zabransky, D. J., Cochran, R. L., Wong, H. Y., Toro, P. V., Cidado, J. R., Croessmann, S., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0943 · Cited by 184
Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience
Schwaederle, M. C., Parker, B. A., Schwab, R. B., Daniels, G. A., Piccioni, D. E., Kesari, S., Helsten, T. L., Bazhenova, L. A., Romero, J., Fanta, P. T., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0795 · Cited by 184
Pietrantonio, F., Vernieri, C., Siravegna, G., Mennitto, A., Berenato, R., Perrone, F., Gloghini, A., Tamborini, E., Lonardi, S., Morano, F., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1863 · Cited by 182
Self-citationDigital PCR analysis of circulating nucleic acids
Hudecova, I. (2015) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2015.03.015 · Cited by 181
Nanomaterial-induced ferroptosis for cancer specific therapy
Liu, M., Liu, B., Liu, Q., Du, K., Wang, Z., & He, N. (2019) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2018.12.015 · Cited by 180
Peeters, D. J. E., Laere, B. D., den Eynden, G. G. V., Laere, S. V., Rothé, F., Ignatiadis, M., Sieuwerts, A. M., Lambrechts, D., Rutten, A., van Dam, P. A., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.92 · Cited by 179
Herpers, B., Eppink, B., James, M. I., Cortina, C., Cañellas-Socias, A., Boj, S. F., Hernando-Momblona, X., Glodzik, D., Roovers, R. C., van de Wetering, M., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00359-0 · Cited by 178
Mohan, S., Heitzer, E., Ulz, P., Lafer, I., Lax, S., Auer, M., Pichler, M., Gerger, A., Eisner, F., Höefler, G., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004271 · Cited by 178
Gale, D. G., Lawson, A. R. J., Howarth, K., Madi, M., Durham, B., Smalley, S., Calaway, J. D., Blais, S., Jones, G., Clark, J., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194630 · Cited by 177
Establishment of tumor‐specific copy number alterations from plasma DNA of patients with cancer
Heitzer, E., Auer, M., Hoffmann, E. M., Pichler, M., Gasch, C., Ulz, P., Lax, S., Waldispuehl‐Geigl, J., Mauermann, O., Mohan, S., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28030 · Cited by 176
Circulating tumour cells and cell-free DNA as tools for managing breast cancer
Mattos‐Arruda, L. D., Cortés, J., Santarpia, L., Vivancos, A. P., Tabernero, J. M., Reis-Filho, J. S., & Seoane, J. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.80 · Cited by 176
KRAS gene amplification in colorectal cancer and impact on response to EGFR‐targeted therapy
Valtorta, E., Misale, S., Sartore‐Bianchi, A., Nagtegaal, I. D., Paraf, F., Lauricella, C., Dimartino, V., Hobor, S., Jacobs, B., Ercolani, C., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28106 · Cited by 175
Self-citationKwak, E. L., Ahronian, L. G., Siravegna, G., Mussolin, B., Borger, D. R., Godfrey, J. T., Jessop, N. A., Clark, J. W., Blaszkowsky, L. S., Ryan, D. P., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0748 · Cited by 175
Self-citationJia, S., Zhang, R., Li, Z., & Li, J. (2017) · Oncotarget · doi:10.18632/oncotarget.17184 · Cited by 175
Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.
Hellmann, M. D., Kim, T.-W., Lee, C. B., Goh, B.-C., Miller, W. H., Oh, D.-Y., Jamal, R., Chee, C.-E., Chow, L. Q. M., Gainor, J. F., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz113 · Cited by 174
Toulany, M., & Rodemann, H. P. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.07.003 · Cited by 174
Fribbens, C. V., García-Murillas, I., Beaney, M., Hrebien, S., O’Leary, B., Kilburn, L., Howarth, K., Epstein, M., Green, E., Rosenfeld, N., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx483 · Cited by 171
The potential of liquid biopsies for the early detection of cancer
Heitzer, E., Perakis, S. O., Geigl, J. B., & Speicher, M. R. (2017) · npj Precision Oncology · doi:10.1038/s41698-017-0039-5 · Cited by 170
Lavallée, V., Baccelli, I., Krošl, J., Wilhelm, B. T., Barabé, F., Gendron, P., Boucher, G., Lemieux, S., Marinier, A., Meloche, S., et al. (2015) · Nature Genetics · doi:10.1038/ng.3371 · Cited by 168
Laurent‐Puig, P., Pekin, D., Normand, C., Kotsopoulos, S. K., Nizard, P., Perez‐Toralla, K., Rowell, R. K., Olson, J., Srinivasan, P., Corre, D. L., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0983 · Cited by 166
Therapy-induced APOBEC3A drives evolution of persistent cancer cells
Isozaki, H., Sakhtemani, R., Abbasi, A., Nikpour, N., Stanzione, M., Oh, S., Langenbucher, A., Monroe, S., Su, W., Cabanos, H. F., et al. (2023) · Nature · doi:10.1038/s41586-023-06303-1 · Cited by 168
Acquired resistance to EGFR‐targeted therapies in colorectal cancer
Emburgh, B. O. V., Bianchi, A. S., Nicolantonio, F. D., Siena, S., & Bardelli, A. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.05.003 · Cited by 162
Self-citationTong, J., Tan, S., Zou, F., Yu, J., & Zhang, L. (2016) · Oncogene · doi:10.1038/onc.2016.247 · Cited by 163
Sang, M., Luo, R., Bai, Y., Dou, J., Zhang, Z., Liu, F., Feng, F., Xu, J., & Liu, W. (2019) · Theranostics · doi:10.7150/thno.36283 · Cited by 163
Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality?
Ignatiadis, M., & Dawson, S. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu480 · Cited by 161
Lee, J. Y., Qing, X., Wei, X., Yali, B., Chi, S., Bak, S. H., Lee, H. Y., Sun, J., Lee, S., Ahn, J. S., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.6874 · Cited by 159
Diagnostics based on nucleic acid sequence variant profiling: PCR, hybridization, and NGS approaches
Khodakov, D. A., Wang, C., & Zhang, D. Y. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.005 · Cited by 159
Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer
Siravegna, G., Lazzari, L., Crisafulli, G., Bianchi, A. S., Mussolin, B., Cassingena, A., Martino, C., Lanman, R. B., Nagy, R. J., Fairclough, S. R., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.004 · Cited by 159
Self-citationTjensvoll, K., Lapin, M., Buhl, T., Oltedal, S., Berry, K. S.-O., Gilje, B., Søreide, J. A., Javle, M. M., Nordgård, O., & Smaaland, R. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.11.012 · Cited by 157
Molecular-Targeted Therapies for Epidermal Growth Factor Receptor and Its Resistance Mechanisms
Yamaoka, T., Ohba, M., & Ohmori, T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112420 · Cited by 156
Feedback and redundancy in receptor tyrosine kinase signaling: relevance to cancer therapies
Sun, C., & Bernards, R. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.08.010 · Cited by 155
Network quantification of EGFR signaling unveils potential for targeted combination therapy
Klinger, B., Sieber, A., Fritsche‐Guenther, R., Witzel, F., Berry, L., Schumacher, D., Yan, Y., Durek, P., Merchant, M. A., Schäfer, R., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.29 · Cited by 155
Salim, K. Y., Vareki, S. M., Danter, W. R., San‐Marina, S., & Koropatnick, J. D. (2016) · Oncotarget · doi:10.18632/oncotarget.9133 · Cited by 155
Clinical utility of circulating tumor DNA for colorectal cancer
Osumi, H., Shinozaki, E., Yamaguchi, K., & Zembutsu, H. (2019) · Cancer Science · doi:10.1111/cas.13972 · Cited by 153
Trial Watch: Monoclonal antibodies in cancer therapy
Galluzzi, L., Vacchelli, E., Fridman, W. H., Galon, J., Sautès‐Fridman, C., Tartour, É., Zucman‐Rossi, J., Zitvogel, L., & Kroemer, G. (2012) · OncoImmunology · doi:10.4161/onci.1.1.17938 · Cited by 152
Normanno, N., Cervantes, A. M. R., Ciardiello, F., Luca, A. D., & Pinto, C. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.07.007 · Cited by 152
Berchuck, J. E., Facchinetti, F., Ditoro, D. F., Baiev, I., Majeed, U., Reyes, S., Chen, C. T., Zhang, K., Sharman, R., Usón, P. L. S., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.09.150 · Cited by 152
Self-citationSchwaederle, M. C., Husain, H., Fanta, P. T., Piccioni, D. E., Kesari, S., Schwab, R. B., Banks, K. C., Lanman, R. B., Talasaz, A. H., Parker, B. A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7110 · Cited by 151
Morganti, S., Tarantino, P., Ferraro, E., D’Amico, P., Viale, G., Trapani, D., Duso, B. A., & Curigliano, G. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.11.008 · Cited by 151
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
