Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients
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INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. RESULTS: We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). CONCLUSION: A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP.
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Coexpression of pIGF-1R and MMP-7 in RAS wild-type metastatic colorectal cancer predicts worse overall survival after treatment with cetuximab.
“Analyses from two clinical trials confirmed that the coexpression of pIGF-1R and MMP-7 in RAS wild-type mCRC predicts worse OS after treatment with cetuximab [119].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [119]
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Cites
The consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170 · see citing works
Panitumumab–FOLFOX4 Treatment and <i>RAS</i> Mutations in Colorectal Cancer
Douillard, J.-Y., Oliner, K. S., Siena, S., Tabernero, J., Burkes, R., Barugel, M., Humblet, Y., Bodoky, G., Cunningham, D., Jassem, J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305275 · Cited by 2,263 · see citing works
Insulin and insulin-like growth factor signalling in neoplasia
Pollak, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2536 · Cited by 2,059 · see citing works
Venook, A. P., Niedzwiecki, D., Lenz, H.-J., Innocenti, F., Fruth, B., Meyerhardt, J. A., Schrag, D., Greene, C., O'Neil, B. H., Atkins, J. N., et al. (2017) · JAMA · doi:10.1001/jama.2017.7105 · Cited by 898 · see citing works
Lesina, M., Kurkowski, M. U., Ludes, K., Rose-John, S., Treiber, M., Klöppel, G., Yoshimura, A., Reindl, W., Sipos, B., Akira, S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.009 · Cited by 862 · see citing works
Arnold, D., Lueza, B., Douillard, J.-Y., Peeters, M., Lenz, H., Venook, A. P., Heinemann, V., Cutsem, E. V., Pignon, J., Tabernero, J. M., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx175 · Cited by 837 · see citing works
Van Cutsem, E., Lenz, H.-J., Köhne, C.-H., Heinemann, V., Tejpar, S., Melezínek, I., Beier, F., Stroh, C., Rougier, P., van Krieken, J. H., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.4812 · Cited by 789 · see citing works
De Sousa E Melo, F., Wang, X., Jansen, M., Fessler, E., Trinh, A., de Rooij, L. P. M. H., de Jong, J. H., de Boer, O. J., van Leersum, R., Bijlsma, M. F., et al. (2013) · Nature Medicine · doi:10.1038/nm.3174 · Cited by 771 · see citing works
IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis
Rokavec, M., Öner, M. G., Li, H., Jackstadt, R., Jiang, L., Lodygin, D., Kaller, M., Horst, D., Ziegler, P. K., Schwitalla, S., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci73531 · Cited by 753 · see citing works
Becht, E., de Reyniès, A., Giraldo, N. A., Pilati, C., Buttard, B., Lacroix, L., Selves, J., Sautès-Fridman, C., Laurent-Puig, P., & Fridman, W. H. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2879 · Cited by 590 · see citing works
Dallas, N. A., Xia, L., Fan, F., Gray, M. J., Gaur, P., Buren, G. V., Samuel, S., Kim, M. P., Lim, S. J., & Ellis, L. M. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2023 · Cited by 573 · see citing works
Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression
Fukuda, A., Wang, S. C., Morris, J. P., Folias, A. E., Liou, A., Kim, G. E., Akira, S., Boucher, K., Firpo, M., Mulvihill, S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.03.002 · Cited by 531 · see citing works
STAT3 Is Necessary for Proliferation and Survival in Colon Cancer–Initiating Cells
Lin, L., Liu, A., Peng, Z., Lin, H.-J. L., Li, P., Li, C., & Lin, J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4660 · Cited by 297 · see citing works
The Role of the Insulin-like Growth Factor System in Human Cancer
Werner, H., & LeRoith, D. (1996) · Advances in cancer research · doi:10.1016/s0065-230x(08)60354-1 · Cited by 296 · see citing works
Regulation of STAT3 by Direct Binding to the Rac1 GTPase
Simon, A. R., Vikis, H. G., Stewart, S., Fanburg, B. L., Cochran, B., & Guan, K. (2000) · Science · doi:10.1126/science.290.5489.144 · Cited by 224 · see citing works
Schneider‐Merck, T., van Bueren, J. J. L., Berger, S., Rossen, K., van Berkel, P. H. C., Derer, S., Beyer, T. D., Lohse, S., Bleeker, W. K., Peipp, M., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900847 · Cited by 223 · see citing works
Trinh, A., Trumpi, K., De Sousa E Melo, F., Wang, X., de Jong, J. H., Fessler, E., Kuppen, P. J. K., Reimers, M. S., Swets, M., Koopman, M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0680 · Cited by 180 · see citing works
Sánchez‐López, E., Flashner-Abramson, E., Shalapour, S., Zhong, Z., Taniguchi, K., Levitzki, A., & Karin, M. (2015) · Oncogene · doi:10.1038/onc.2015.326 · Cited by 162 · see citing works
TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype
Fessler, E., Drost, J., van Hooff, S. R., Linnekamp, J. F., Wang, X., Jansen, M., De Sousa E Melo, F., Prasetyanti, P. R., IJspeert, J. E., Franitza, M., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606184 · Cited by 159 · see citing works
Miyamoto, S., Yano, K., Sugimoto, S., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1916 · Cited by 153 · see citing works
Nakamura, M., Miyamoto, S., Maeda, H., et al. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.06.010 · Cited by 128 · see citing works
Yao, C., Su, L., Shan, J., Zhu, C., Liu, L., Liu, C., Xu, Y., Yang, Z., Bian, X., Shao, J., et al. (2016) · Stem Cells · doi:10.1002/stem.2320 · Cited by 123 · see citing works
Hemers, E., Duval, C., McCaig, C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0157 · Cited by 98 · see citing works
Girnita, L., Girnita, A., Brodin, B. A., Xie, Y., Nilsson, G. P., Dricu, A., Lundeberg, J., Wejde, J., Bartolazzi, A., Wiman, K. G., et al. (2000) · PubMed · Cited by 85 · see citing works
Williams, A. C., Smartt, H., H-Zadeh, A., MacFarlane, M., Paraskeva, C., & Collard, T. J. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401919 · Cited by 67 · see citing works
Miyamoto, S., Nakamura, M., Yano, K., et al. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00448.x · Cited by 55 · see citing works
Immune biomarkers of anti-EGFR monoclonal antibody therapy
Trivedi, S., Concha‐Benavente, F., Srivastava, R. M., Jie, H., Gibson, S. P., Schmitt, N. C., & Ferris, R. L. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu156 · Cited by 49 · see citing works
Neoadjuvant chemotherapy affects molecular classification of colorectal tumors
Trumpi, K., Ubink, I., Trinh, A., Djafarihamedani, M., Jongen, J. M., Govaert, K. M., Elias, S. G., van Hooff, S. R., Medema, J. P., Lacle, M. M., et al. (2017) · Oncogenesis · doi:10.1038/oncsis.2017.48 · Cited by 46 · see citing works
Adachi, Y., Li, R., Yamamoto, H., et al. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp134 · Cited by 44 · see citing works
Customizing The Targeting of IGF-1 Receptor
Baserga, R. (2009) · Future Oncology · doi:10.2217/14796694.5.1.43 · Cited by 36 · see citing works
Gallego, R., Codony‐Servat, J., García‐Albéniz, X., Carcereny, E., Longarón, R., Oliveras, A., Tosca, M., Auge, J. M., Gascón, P., & Maurel, J. (2008) · Endocrine Related Cancer · doi:10.1677/erc-08-0250 · Cited by 32 · see citing works
Self-citationNadal, C., Maurel, J., Gallego, R., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2119 · Cited by 29 · see citing works
Self-citationHorndler, C., Gallego, R., García‐Albéniz, X., et al. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.13839 · Cited by 7 · see citing works
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Zhou, J., Ji, Q., & Li, Q. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02130-2 · Cited by 246 · see citing works
- Authors
- Alonso, V., Escudero, P., Fernández-Martos, C., Salud, A., Méndez, M., Gallego, J., Rodriguez, J.-R., Martín-Richard, M., Fernández-Plana, J., Manzano, H., Méndez, J.-C., Zanui, M., Falcó, E., Gil-Raga, M., Rojo, F., Cuatrecasas, M., Feliu, J., García-Albéniz, X., & Maurel, J.
- Affiliations
- Hospital Universitario Miguel Servet (ES)
- Hospital Clínico Universitario Lozano Blesa (ES)
- Fundación Instituto Valenciano de Oncología (ES)
- Hospital Universitario de Móstoles (ES)
- Government of Extremadura (ES)
- Hospital de Sant Pau (ES)
- University Hospital Mútua de Terrassa (ES)
- Hospital Universitario Son Espases (ES)
- Hospital de Mataró (ES)
- Hospital Son Llatzer (ES)
- Hospital de Sagunto (ES)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- Hospital Clínic de Barcelona (ES)
- Corresponding author
- Maurel, Joan
- ORCID
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 20
- Issue
- 7
- Pages
- 678-686
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC6030389
- OpenAlex
- W2804505521
- Cited by
- 10
- References
- 33
- Citations by year
- 2025: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, cc-by-nc-nd)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, cc-by-nc-nd)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Docusalut (Conselleria de Salut i Consum del Govern de les Illes Balears) (submittedVersion, cc-by-nc-nd)
- Hispana (submittedVersion, cc-by-nc-nd)
- Repositori ObertUDL (University of Lleida) (submittedVersion, cc-by-nc-nd)
- Funders
- Amgen
- Merck
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- MMP-7, KRAS wild-type, metastatic colorectal cancer, panitumumab, cetuximab, anti-EGFR therapy, FOLFOX6, FOLFIRI, overall survival, progression-free survival, predictive biomarkers
- MeSH terms
- Cetuximab, Panitumumab, Aged, Antibodies, Monoclonal, Female, Humans, Male, Middle Aged, Mutation, Prognosis, Colorectal Neoplasms, Gene Expression, Proportional Hazards Models, Receptor, IGF Type 1, ras Proteins, Matrix Metalloproteinase 7, Proto-Oncogene Proteins B-raf, Kaplan-Meier Estimate
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