PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

Frattini, M; Saletti, P; Romagnani, E; Martin, V; Molinari, F; Ghisletta, M; Camponovo, A; Etienne, L L; Cavalli, F; Mazzucchelli, L

doi:10.1038/sj.bjc.6604009

Cited by 540Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsHER2/EGFR in Cancer Research

PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

Open access

Frattini, M, Saletti, P, Romagnani, E, Martin, V, Molinari, F, Ghisletta, M, Camponovo, A, Etienne, L L +2 more·2007·British Journal of Cancer

DOI 10.1038/sj.bjc.6604009PMC PMC2360431

Open this paper in CoChat — free account Open PDF

Abstract

To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients. Twenty-seven cetuximab-treated mCRC patients were evaluated for drug response and investigated for EGFR protein expression and gene status, K-Ras mutational status and PTEN protein expression. Ten patients achieved a partial response (PR) to cetuximab-based therapy. All 27 patients showed EGFR protein overexpression. Epidermal growth factor receptor gene amplification was observed in eight out of 27 (30%) and chromosome 7 marked polysomy in 16 (59%) patients. Partial response was observed in six out of eight patients with EGFR gene amplification, four out of 16 with marked polysomy and none out of three with eusomy (P<0.05). The K-Ras wild-type sequence was observed in 17 patients, and nine of them experienced a PR. Conversely, K-Ras was mutated in 10 cases, of which one patient experienced a PR (P<0.05). The PTEN protein was normally expressed in 16 patients, and 10 of them achieved a PR. In contrast, no benefit was documented in 11 patients with loss of PTEN activity (P<0.001). Patients with EGFR gene amplification or chromosome 7 marked polysomy respond to cetuximab. In addition to K-Ras mutations, we demonstrate for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab.

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

Crossref · 10.1038/sj.bjc.6604009

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

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?

PTEN inactivation is associated with nonresponsiveness to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.
“PTEN inactivation (usually assessed as lack of protein expression) has been associated with nonresponsiveness to anti-EGFR moAbs in mCRC patients in several studies [19, 73, 75, 76]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [75]
Patients with PTEN-negative status showed a worse response rate and shorter progression-free survival than those with PTEN-positive status.
“Patients with PTEN-negative status showed a worse response rate and shorter progression-free survival (PFS) than those with PTEN-positive status [106, 108, 109].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [109]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132 · see citing works
Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer
Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., Bets, D., Mueser, M., Harstrick, A., Verslype, C., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033025 · Cited by 5,035 · see citing works
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Lièvre, A., Bachet, J.-B., Le Corre, D., Boige, V., Landi, B., Emile, J.-F., Côté, J.-F., Tomasic, G., Penna, C., Ducreux, M., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0191 · Cited by 2,229 · see citing works
Phase II Trial of Cetuximab in Patients With Refractory Colorectal Cancer That Expresses the Epidermal Growth Factor Receptor
Saltz, L. B., Meropol, N. J., Loehrer, P. J., Needle, M. N., Kopit, J., & Mayer, R. J. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.10.182 · Cited by 1,694 · see citing works
Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry.
Chung, K. Y., Shia, J., Kemeny, N. E., Shah, M., Schwartz, G. K., Tse, A., Hamilton, A., Pan, D., Schrag, D., Schwartz, L., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.08.037 · Cited by 1,081 · see citing works
Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study
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 · see citing works
PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma
Saal, L. H., Holm, K., Maurer, M. S., Memeo, L., Su, T., Wang, X., Yu, J. S., Malmström, P.-O., MANSUKHANI, M. M., Enoksson, J., et al. (2005) · Cancer Research · doi:10.1158/0008-5472-can-04-3913 · Cited by 877 · see citing works
Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy
Di Fiore, F., Blanchard, F., Charbonnier, F., Le Pessot, F., Lamy, A., Galais, M. P., Bastit, L., Killian, A., Sesboüé, R., Tuech, J. J., et al. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603685 · Cited by 734 · see citing works
The EGFR as a target for anticancer therapy—focus on cetuximab
Baselga, J. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00233-7 · Cited by 566 · see citing works
Multicenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines
Lenz, H., Cutsem, E. V., Khambata‐Ford, S., Mayer, R. J., Gold, P. J., Stella, P. J., Mirtsching, B. C., Cohn, A. L., Pippas, A. W., Azarnia, N., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.7595 · Cited by 522 · see citing works
The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, andmdr gene expression in colorectal cancer
Mayer, A., Takimoto, M., Fritz, E., Schellander, G., Kofler, K., & Ludwig, H. (1993) · Cancer · doi:10.1002/1097-0142(19930415)71:8 · Cited by 413 · see citing works
Immunohistochemical Detection of EGFR in Paraffin-embedded Tumor Tissues
Atkins, D., Reiffen, K. A., Tegtmeier, C., Winther, H., Bonato, M., & Störkel, S. (2004) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.3a6195.2004 · Cited by 319 · see citing works
Epidermal Growth Factor Receptor (EGFR) Status in Primary Colorectal Tumors Does Not Correlate With EGFR Expression in Related Metastatic Sites: Implications for Treatment With EGFR-Targeted Monoclonal Antibodies
Scartozzi, M., Bearzi, I., Berardi, R., Mandolesi, A., Fabris, G., & Cascinu, S. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.00.117 · Cited by 249 · see citing works
Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma
Folprecht, G., Lutz, M. P., Schöffski, P., Seufferlein, T. T. W., Nolting, A., Pollert, P., & Köhne, C.-H. (2005) · Annals of Oncology · doi:10.1093/annonc/mdj084 · Cited by 234 · see citing works
Different Genetic Features Associated with Colon and Rectal Carcinogenesis
Frattini, M., Balestra, D., Suardi, S., Oggionni, M., Alberici, P., Radice, P., Costa, A., Daidone, M. G., Leo, E., Pilotti, S., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0031 · Cited by 228 · see citing works
Self-citation
Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigation
Thomas, S. M., & Grandis, J. R. (2003) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2003.10.003 · Cited by 174 · see citing works
Breast Cancer — Loss of PTEN Predicts Resistance to Treatment
Pandolfi, P. P. (2004) · New England Journal of Medicine · doi:10.1056/nejmcibr043143 · Cited by 167 · see citing works
Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer: An international phase II study
Rubio, E., Tabernero, J. M., Cutsem, E. V., Cervantes, A. M. R., André, T., Humblet, Y., Soulié, P., Corretgé, S., Kisker, O., & de Gramont, A. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.23.16_suppl.3535 · Cited by 155 · see citing works
Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK
Borner, M., Koeberle, D., Von Moos, R., Saletti, P., Rauch, D., Hess, V., Trojan, A., Helbling, D., Pestalozzi, B., Caspar, C., et al. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn058 · Cited by 124 · see citing works
Self-citation
Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results
Venook, A. P., Niedzwiecki, D., Hollis, D. R., Sutherland, S., Goldberg, R. M., Alberts, S. R., Benson, A. B., Wade, J. L., Schilsky, R. L., & Mayer, R. J. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.3509 · Cited by 116 · see citing works
Cetuximab Plus Irinotecan in Heavily Pretreated Metastatic Colorectal Cancer Progressing on Irinotecan: MABEL Study
Wilke, H., Glynne‐Jones, R., Thaler, J., Adenis, A., Preusser, P., Aranda, E., Aapro, M., Esser, R., Loos, A. H., & Siena, S. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.3758 · Cited by 104 · see citing works
Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan and oxaliplatin
Lenz, H., Mayer, R. J., Gold, P. J., Mirtsching, B. C., Stella, P. J., Cohn, A. L., Pippas, A. W., Azarnia, N., Needle, M. N., & Cutsem, E. V. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.22.90140.3510 · Cited by 102 · see citing works
An international phase II study of cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with metastatic colorectal cancer (CRC) expressing Epidermal Growth Factor Receptor (EGFR). Preliminary results
Tabernero, J. M., Cutsem, E. V., Sastre, J., Cervantes, A. M. R., Laethem, J. V., Humblet, Y., Soulié, P., Corretgé, S., Mueser, M., & de Gramont, A. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.22.90140.3512 · Cited by 76 · see citing works
Pitfalls in immunohistochemical assessment of EGFR expression in soft tissue sarcomas
Kersting, C., Packeisen, J., Leidinger, B., Brandt, B., von Wasielewski, R., Winkelmann, W., van Diest, P. J., Gosheger, G., & Buerger, H. (2006) · Journal of Clinical Pathology · doi:10.1136/jcp.2005.028373 · Cited by 60 · see citing works
Are heterogenous results of EGFR immunoreactivity in renal cell carcinoma related to non-standardised criteria for staining evaluation?
Langner, C., Ratschek, M., Rehak, P., Schips, L., & Zigeuner, R. E. (2004) · Journal of Clinical Pathology · doi:10.1136/jcp.2003.015743 · Cited by 50 · see citing works
Phosphatase Protein Homologue to Tensin Expression and Phosphatidylinositol-3 Phosphate Kinase Mutations in Colorectal Cancer
Frattini, M., Signoroni, S., Pilotti, S., Bertario, L., Benvenuti, S., Zanon, C., Bardelli, A., & Pierotti, M. A. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2780 · Cited by 47 · see citing works
Self-citation
Association Between Recurrence of Sporadic Colorectal Cancer, High Level of Microsatellite Instability, and Loss of Heterozygosity at Chromosome 18q
Sarli, L., Bottarelli, L., Bader, G., Iusco, D. R., Pizzi, S., Costi, R., D’Adda, T., Bertolani, M., Roncoroni, L., & Bordi, C. (2004) · Diseases of the Colon & Rectum · doi:10.1007/s10350-004-0628-6 · Cited by 45 · see citing works
MABEL—A large multinational study of cetuximab plus irinotecan in irinotecan resistant metastatic colorectal cancer
Wilke, H., Glynne‐Jones, R., Thaler, J., Adenis, A., Preusser, P., Aguilar, E. A., Aapro, M., Berg, N. V. D., Eggleton, S. P., & Siena, S. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.3549 · Cited by 33 · see citing works
The impact of cetuximab on the capecitabine plus oxaliplatin (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC): A randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)
Borner, M., Mingrone, W. B., Koeberle, D., von Moos, R., Rauch, D., Saletti, P., Herrmann, R. P., Dietrich, D., Lanz, D., & Roth, A. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.3551 · Cited by 26 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

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 · see citing works
EGFR Antagonists in Cancer Treatment
Ciardiello, F., & Tortora, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707704 · Cited by 2,063 · see citing works
Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
Di Nicolantonio, F., Martini, M., Molinari, F., Sartore-Bianchi, A., Arena, S., Saletti, P., De Dosso, S., Mazzucchelli, L., Frattini, M., Siena, S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0786 · Cited by 1,591 · see citing works
Self-citation
American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy
Allegra, C. J., Jessup, J. M., Somerfield, M. R., Hamilton, S. R., Hammond, E. H., Hayes, D. F., McAllister, P. K., Morton, R. F., & Schilsky, R. L. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.21.9170 · Cited by 1,156 · see citing works
Molecular 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 · see citing works
Association of KRAS p.G13D Mutation with Outcome in Patients with Chemotherapy-Refractory Metastatic Colorectal Cancer Treated with Cetuximab
De Roock, W., Jonker, D. J., Di Nicolantonio, F., Sartore-Bianchi, A., Tu, D., Siena, S., Lamba, S., Arena, S., Frattini, M., Piessevaux, H., et al. (2010) · JAMA · doi:10.1001/jama.2010.1535 · Cited by 748 · see citing works
“KRAS mutation analysis was performed by direct sequencing as described previously.(6-8) All patients in the Leuven and Italian datasetsprovidedwritten informedconsenttotheoriginalclinicaltrialandtomolecular analyses.”
MethodSelf-citation
Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer
Linardou, H., Dahabreh, I. J., Kanaloupiti, D., Siannis, F., Bafaloukos, D., Kosmidis, P., Papadimitriou, C. A., & Murray, S. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70206-7 · Cited by 739 · see citing works
PIK3CA Mutations in Colorectal Cancer Are Associated with Clinical Resistance to EGFR-Targeted Monoclonal Antibodies
Sartore-Bianchi, A., Martini, M., Molinari, F., Veronese, S., Nichelatti, M., Artale, S., Di Nicolantonio, F., Saletti, P., De Dosso, S., Mazzucchelli, L., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2466 · Cited by 739 · see citing works
“In CRC, we have previously reported that loss of PTEN expression, which occurs in 30% of sporadic cases, may be associated with lack of response to cetuximab (16).”
BackgroundMethodSelf-citation
Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer
Laurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6796 · Cited by 673 · see citing works
KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer
Roock, W. D., de Vriendt, V., Normanno, N., Ciardiello, F., & Tejpar, S. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70209-6 · Cited by 605 · see citing works
Epidermal growth factor receptor targeting in cancer: a review of trends and strategies
Yewale, C., Baradia, D., Vhora, I., Patil, S., & Misra, A. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.07.100 · Cited by 533 · see citing works
“Two other reported response predictors, namely PI3KCA mutation and PTEN inactivation, also contribute to the resistance to mAbs in colorectal cancer [201,202].”
Background
Resistance to anti-EGFR therapy in colorectal cancer: From heterogeneity to convergent evolution
Misale, S., Di Nicolantonio, F., Sartore-Bianchi, A., Siena, S., & Bardelli, A. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0462 · Cited by 513 · see citing works
Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling
Korkaya, H., Paulson, A., Charafe-Jauffret, E., Ginestier, C., Brown, M., Dutcher, J., Clouthier, S. G., & Wicha, M. S. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000121 · Cited by 523 · see citing works
“The PTEN/ PI3-K/Akt pathway has been described as a major pathway conferring resistance to conventional therapies in multiple tumor types [15–17].”
Background
Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor–Targeted Therapy in Metastatic Colorectal Cancer
Siena, S., Bianchi, A. S., Nicolantonio, F. D., Balfour, J., & Bardelli, A. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djp280 · Cited by 526 · see citing works
Impact of FcγRIIa-FcγRIIIa Polymorphisms and KRAS Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan
Bibeau, F., Lopez-Crapez, E., Di Fiore, F., Thezenas, S., Ychou, M., Blanchard, F., Lamy, A., Penault-Llorca, F., Frébourg, T., Michel, P., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0463 · Cited by 521 · see citing works
Pharmacologic resistance in colorectal cancer: a review
Hammond, W. A., Swaika, A., & Mody, K. (2015) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834015614530 · Cited by 520 · see citing works
PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab.
Jhawer, M., Goel, S., Wilson, A. J., Montagna, C., Ling, Y.-H., Byun, D.-S., Nasser, S., Arango, D., Shin, J., Klampfer, L., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5659 · Cited by 460 · see citing works
Implications for KRAS status and EGFR-targeted therapies in metastatic CRC
Normanno, N., Tejpar, S., Morgillo, F., De Luca, A., Van Cutsem, E., & Ciardiello, F. (2009) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.111 · Cited by 436 · see citing works
Prevalence and Heterogeneity of KRAS, BRAF, and PIK3CA Mutations in Primary Colorectal Adenocarcinomas and Their Corresponding Metastases
Baldus, S. E., Schaefer, K.-L., Engers, R., Hartleb, D., Stoecklein, N. H., & Gabbert, H. E. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2446 · Cited by 432 · see citing works
PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients
Perrone, F., Lampis, A., Orsenigo, M., Di Bartolomeo, M., Gevorgyan, A., Losa, M., Frattini, M., Riva, C., Andreola, S., Bajetta, E., et al. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn541 · Cited by 410 · see citing works
“However, the nondefinitive role of EGFR gene copy number as a biomarker capable of identifying cetuximabresponsive patients implies that patients without any signs of EGFR signalling pathway activation (50% of our cohort) should not be denied access to anti-EGFR treatment because they may respond to cetuximab [2, 4, 5…”
BackgroundMethodResultInfluentialSelf-citation
PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer.
Loupakis, F., Pollina, L., Stasi, I., Ruzzo, A., Scartozzi, M., Santini, D., Masi, G., Graziano, F., Cremolini, C., Rulli, E., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.2796 · Cited by 403 · see citing works
The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis
Therkildsen, C., Bergmann, T. K., Schnack, T. H., Ladelund, S., & Nilbert, M. C. (2014) · Acta Oncologica · doi:10.3109/0284186x.2014.895036 · Cited by 392 · see citing works
Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W. W., Cushman‐Vokoun, A. M., Funkhouser, W. K., Kopetz, S., Lieu, C. H., Lindor, N. M., Minsky, B. D., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.9807 · Cited by 365 · see citing works
The role of PTEN signaling perturbations in cancer and in targeted therapy
Keniry, M. E., & Parsons, R. E. (2008) · Oncogene · doi:10.1038/onc.2008.248 · Cited by 358 · see citing works
Association of KRAS G13D Tumor Mutations With Outcome in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab
Tejpar, S., Celik, I., Schlichting, M., Sartorius, U., Bokemeyer, C., & Van Cutsem, E. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.2592 · Cited by 353 · see citing works
Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus
Nicolantonio, F. D., Arena, S., Tabernero, J. M., Grosso, S., Molinari, F., Macarulla, T. M., Russo, M., Cancelliere, C., Zecchin, D., Mazzucchelli, L., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci37539 · Cited by 343 · see citing works
“tions was performed and evaluated according to the literature (38).”
MethodSelf-citation
A perspective on anti-EGFR therapies targeting triple-negative breast cancer.
Nakai, K., Hung, M., & Yamaguchi, H. (2016) · Europe PMC (PubMed Central) · Cited by 324 · see citing works
KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program
van Krieken, J. H., Jung, A., Kirchner, T., Carneiro, F., Seruca, R., Bosman, F. T., Quirke, P., Fléjou, J., Hansen, T. P., Hertogh, G. D., et al. (2008) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-008-0665-y · Cited by 289 · see citing works
“The loss of PTEN protein expression negatively predicts efficacy of cetuximab therapy in patients with metastatic colorectal cancer [50].”
Background
Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab
Brand, T. M., Iida, M., & Wheeler, D. L. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.9.15050 · Cited by 275 · see citing works
Analysis of Potential Predictive Markers of Cetuximab Benefit in BMS099, a Phase III Study of Cetuximab and First-Line Taxane/Carboplatin in Advanced Non–Small-Cell Lung Cancer
Khambata‐Ford, S., Harbison, C. T., Hart, L. L., Awad, M., Xu, L., Horak, C. E., Dakhil, S. R., Hermann, R. C., Lynch, T. J., & Weber, M. R. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.2890 · Cited by 265 · see citing works
“Absence of PTEN (a downstream negative regulator of EGFR signaling) may be associated with cetuximab resistance in mCRC.(47,48) Evidence from SWOG 0342 and 0536, as well as from the BR.”
Background
Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer
Sartore-Bianchi, A., Di Nicolantonio, F., Nichelatti, M., Molinari, F., De Dosso, S., Saletti, P., Martini, M., Cipani, T., Marrapese, G., Mazzucchelli, L., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007287 · Cited by 259 · see citing works
“We and others have previously shown that loss of PTEN expression, which occurs in 30% of sporadic cases, is associated with lack of response to cetuximab [24], and that PIK3CA/PTEN deregulation may be a biomarker of resistance in KRAS wild-type patients [25,26] and cellular models of CRC [27].”
BackgroundMethodSelf-citation
Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies
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
Therapeutic Targeting of Cancers with Loss of PTEN Function
Dillon, L. M., & Miller, T. W. (2014) · Current Drug Targets · doi:10.2174/1389450114666140106100909 · Cited by 240 · see citing works
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 242 · see citing works
Metastatic Colorectal Cancer: From Improved Survival to Potential Cure
Gallagher, D. J., & Kemeny, N. E. (2010) · Oncology · doi:10.1159/000315730 · Cited by 237 · see citing works
Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy
Sierra, J. R., Cepero, V., & Giordano, S. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-75 · Cited by 230 · see citing works
Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study
Licitra, L. F., Mesı́a, R., Rivera, F., Remenár, É., Hitt, R., Erfan, J., Rottey, S., Kawecki, A., Zabolotnyy, D., Benasso, M., et al. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq588 · Cited by 226 · see citing works
“While some studies reported an association of high EGFR gene copy number and improved outcome in mCRC and NSCLC patients receiving cetuximab [10–14], other studies failed to identify similar associations [15–17].”
Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?
Santini, D., Vincenzi, B., Addeo, R., Garufi, C., Masi, G., Scartozzi, M., Mancuso, A. P., Frezza, A. M., Venditti, O., Imperatori, M., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mdr623 · Cited by 211 · see citing works
“Loss of phosphatase and tensin homolog protein, a negative regulator of PI3K, has also been associated with resistance to anti-EGFR therapy [20–22].”
Background
Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab
Tol, J., Dijkstra, J. R., Klomp, M., Teerenstra, S., Dommerholt, M., Vink-Börger, M. E., van Cleef, P. H. J., van Krieken, J. H., Punt, C. J. A., & Nagtegaal, I. D. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.03.036 · Cited by 210 · see citing works
Colorectal Cancer Biomarkers: Where Are We Now?
González‐Pons, M., & Cruz-Correa, M. R. (2015) · BioMed Research International · doi:10.1155/2015/149014 · Cited by 210 · see citing works
Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR
Heinemann, V., Stintzing, S., Kirchner, T., Boeck, S. H., & Jung, A. (2008) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2008.11.005 · Cited by 203 · see citing works
KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803
Ogino, S., Meyerhardt, J. A., Irahara, N., Niedzwiecki, D., Hollis, D. R., Saltz, L. B., Mayer, R. J., Schaefer, P., Whittom, R., Hantel, A., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1570 · Cited by 197 · see citing works
KRAS and BRAF Mutations Predict Primary Resistance to Imatinib in Gastrointestinal Stromal Tumors
Miranda, C., Nucifora, M., Molinari, F., Conca, E., Anania, M. C., Bordoni, A., Saletti, P., Mazzucchelli, L., Pilotti, S., Pierotti, M. A., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2230 · Cited by 182 · see citing works
“Furthermore, mutational analyses were conducted using widely accepted protocols (15, 16).”
MethodSelf-citation
HGF Rescues Colorectal Cancer Cells from EGFR Inhibition via MET Activation
Liska, D., Chen, C.-T., Bachleitner-Hofmann, T., Christensen, J. G., & Weiser, M. R. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0568 · Cited by 176 · see citing works
“Similarly, activating mutations in the PIK3CA p110 subunit and inactivation of the PTEN phosphatase (which can occur parallel to KRAS or BRAF mutations) have also been shown to be associated with cetuximab resistance (21-25).”
Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W. W., Cushman‐Vokoun, A. M., Funkhouser, W. K., Kopetz, S., Lieu, C. H., Lindor, N. M., Minsky, B. D., et al. (2017) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2016-0554-cp · Cited by 176 · see citing works
Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways
McCubrey, J. A., Steelman, L. S., Kempf, C., Chappell, W. H., Abrams, S. L., Stivala, F., Malaponte, G., Nicoletti, F., Libra, M., Bäsecke, J., et al. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22647 · Cited by 173 · see citing works
“There is also a poorer response to Herceptin (trastuzumab) in combination with taxane in PTEN-deficient tumors (Nagata et al., 2004; Frattini et al., 2007).”
Background
Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer
Dahabreh, I. J., Terasawa, T., Castaldi, P. J., & Trikalinos, T. A. (2011) · Annals of Internal Medicine · doi:10.7326/0003-4819-154-1-201101040-00006 · Cited by 169 · see citing works
“…et al, 2007 (57) Moroni et al, 2005 (52) Sartore-Bianchi et al, 2009 (79) Van Cutsem et al, 2009 (16) Di Nicolantonio et al, 2008 (60) Frattini et al, 2007 (56) Graziano et al, 2010 (83)Garm Spindler et al, 2009 (67) Loupakis et al, 2009 (70) Loupakis et al, 2009 (71) Bokemeyer et…”
A Review of the Most Promising Biomarkers in Colorectal Cancer: One Step Closer to Targeted Therapy
Deschoolmeester, V., Baay, M. F. D., Specenier, P. M., Lardon, F., & Vermorken, J. B. (2010) · The Oncologist · doi:10.1634/theoncologist.2010-0025 · Cited by 168 · see citing works
The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer
Eklöf, V., Wikberg, M. L., Edin, S., Dahlin, A. M., Jonsson, B.-A., Öberg, Å., Rutegård, M., & Palmqvist, R. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.212 · Cited by 165 · see citing works
“PIK3CA and PTEN have been suggested to harbour aberrations in 30–40% of all sporadic CRC cases (Samuels and Ericson, 2006; Frattini et al, 2007), which might explain part of this resistance.”
Background
Functions and Regulation of the PTEN Gene in Colorectal Cancer
Molinari, F., & Frattini, M. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2013.00326 · Cited by 162 · see citing works
“A preliminary work on a retrospective series of patients reported that loss of PTEN expression, observed in 40% of primary tumor in mCRC patients, was significantly associated with non-responsiveness to cetuximab (44).”
BackgroundSelf-citation
HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients
Martin, V, Landi, L., Molinari, F., Fountzilas, G., Geva, R., Riva, A., Saletti, P., De Dosso, S., Spitale, A., Tejpar, S., et al. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.4 · Cited by 156 · see citing works
“Some of the data on partial cohorts have been previously published for other purposes (Frattini et al, 2007; Personeni et al, 2008; De Roock et al, 2010).”
BackgroundMethodInfluentialSelf-citation
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 160 · see citing works
“…SartoreBianchi et al., 2009); amplification of HER2 (Bertotti et al., 2011), MET (Bardelli et al., 2013), and KRAS (Smith et al., 2010; Valtorta et al., 2013); and loss of PTEN expression (Frattini et al., 2007), all of which are components of or interact with the EGFR signal transduction pathway.”
Background
Increased Detection Sensitivity for KRAS Mutations Enhances the Prediction of Anti-EGFR Monoclonal Antibody Resistance in Metastatic Colorectal Cancer
Molinari, F., Felicioni, L., Buscarino, M., De Dosso, S., Buttitta, F., Malatesta, S., Movilia, A., Luoni, M., Boldorini, R., Alabiso, O., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3137 · Cited by 159 · see citing works
“Furthermore, mutational analyses were performed using widely accepted protocols (4, 17), and the laboratory”
BackgroundMethodInfluentialSelf-citation
PIK3CA, BRAF, and PTEN Status and Benefit from Cetuximab in the Treatment of Advanced Colorectal Cancer—Results from NCIC CTG/AGITG CO.17
Karapetis, C. S., Jonker, D. J., Daneshmand, M., Hanson, J. E. L., O'Callaghan, C. J., Marginean, C. E., Zalcberg, J. R., Simes, J. R., Moore, M. J., Tebbutt, N. C., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0606 · Cited by 158 · see citing works
“monoclonal antibodies in patients with metastatic colorectal cancer (25, 31, 37).”
Molecular Biomarkers for the Evaluation of Colorectal Cancer
Sepulveda, A. R., Hamilton, S. R., Allegra, C. J., Grody, W. W., Cushman‐Vokoun, A. M., Funkhouser, W. K., Kopetz, S., Lieu, C. H., Lindor, N. M., Minsky, B. D., et al. (2017) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.11.001 · Cited by 147 · see citing works
PTEN as a Prognostic/Predictive Biomarker in Cancer: An Unfulfilled Promise?
Bazzichetto, C., Conciatori, F., Pallocca, M., Falcone, I., Fanciulli, M., Cognetti, F., Milella, M., & Ciuffreda, L. (2019) · Cancers · doi:10.3390/cancers11040435 · Cited by 145 · see citing works
“demonstrated that PTEN loss in metastases could also be predictive for the combined treatment outcome of cetuximab plus irinotecan [130,131].”
Background
Difluorinated-Curcumin (CDF) Restores PTEN Expression in Colon Cancer Cells by Down-Regulating miR-21
Roy, S., Yu, Y., Padhyé, S., Sarkar, F. H., & Majumdar, A. P. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068543 · Cited by 143 · see citing works
“pathway confers drug resistance to different malignancies including colorectal cancer [5,6,7,8].”
Background
Detection of KRAS and BRAF Mutations in Colorectal Carcinoma
Arcila, M. E., Lau, C., Nafa, K., & Ladanyi, M. (2011) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2010.11.005 · Cited by 137 · see citing works
Prospective Cost-Effectiveness Analysis of Cetuximab in Metastatic Colorectal Cancer: Evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 Trial
Mittmann, N., Au, H., Tu, D., O'Callaghan, C. J., Isogai, P. K., Karapetis, C. S., Zalcberg, J. R., Evans, W. K., Moore, M. J., Siddiqui, J., et al. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djp232 · Cited by 137 · see citing works
The biological properties of cetuximab
Vincenzi, B., Schiavon, G., Silletta, M., Santini, D., & Tonini, G. (2008) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2008.07.006 · Cited by 138 · see citing works
“[107] Frattini M, Saletti P, Romagnani E, et al.”
Background
Quantitative and qualitative characterization of plasma DNA identifies primary and recurrent colorectal cancer
Frattini, M., Gallino, G., Signoroni, S., Balestra, D., Lusa, L., Battaglia, L., Sozzi, G., Bertario, L., Leo, E., Pilotti, S., et al. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.021 · Cited by 136 · see citing works
“to the efficacy of anti-EGFR monoclonal antibodies administration [21–28].”
BackgroundSelf-citation
Mutations and Response to Epidermal Growth Factor Receptor Inhibitors
Laurent‐Puig, P., Lièvre, A., & Blons, H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0905 · Cited by 133 · see citing works
A combined oncogenic pathway signature of BRAF , KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction
Tian, S., Simon, I., Moreno, V., Roepman, P., Tabernero, J., Snel, M., van't Veer, L., Salazar, R., Bernards, R., & Capella, G. (2013) · Gut · doi:10.1136/gutjnl-2012-302423 · Cited by 128 · see citing works
Turning Off AKT: PHLPP as a Drug Target
Newton, A. C., & Trotman, L. C. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140338 · Cited by 131 · see citing works
“Studies have shown that the successful response to several RTK target therapies correlates well with intact PTEN gene status and function (93, 94).”
Background
Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival
Sawai, H., Yasuda, A., Ochi, N., Ma, J., Matsuo, Y., Wakasugi, T., Takahashi, H., Funahashi, H., Sato, M., & Takeyama, H. (2008) · BMC Gastroenterology · doi:10.1186/1471-230x-8-56 · Cited by 129 · see citing works
“List of abbreviations PTEN: phosphatase and tensin homolog; PI3K: phosphatidylinositol 3-kinase; PIP3: phosphoinositol-3,4,5triphosphate; EGFR: epidermal growth factor receptor.”
Background
Implementing prognostic and predictive biomarkers in CRC clinical trials
Schaeybroeck, S. V., Allen, W. L., Turkington, R. C., & Johnston, P. G. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.15 · Cited by 126 · see citing works
Salivary gland carcinomas
Ettl, T., Schwarz‐Furlan, S., Gosau, M., & Reichert, T. E. (2012) · Oral and Maxillofacial Surgery · doi:10.1007/s10006-012-0350-9 · Cited by 126 · see citing works
Impact of KRAS, BRAF, PIK3CA Mutations, PTEN, AREG, EREG Expression and Skin Rash in ≥2nd Line Cetuximab-Based Therapy of Colorectal Cancer Patients
Saridaki, Z., Tzardi, M. N., Papadaki, C., Sfakianaki, M., Pega, F., Kalikaki, A., Tsakalaki, E., Trypaki, M., Messaritakis, I., Stathopoulos, E. N., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015980 · Cited by 127 · see citing works
CETUXIMAB: From Bench to Bedside
Vincenzi, B., Zoccoli, A., Pantano, F., Venditti, O., & Galluzzo, S. (2010) · Current Cancer Drug Targets · doi:10.2174/156800910790980241 · Cited by 125 · see citing works
“evaluated PTEN protein tumor expression in 27 cetuximab-treated mCRC patients and demonstrated for the first time that the loss of PTEN protein expression is associated with non responsiveness to cetuximab [137].”
Background
PIK3CA and PTEN Gene and Exon Mutation-Specific Clinicopathologic and Molecular Associations in Colorectal Cancer
Day, F. L., Jorissen, R. N., Lipton, L. R., Mouradov, D., Sakthianandeswaren, A., Christie, M., Li, S., Tsui, C., Tie, J., Desai, J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3614 · Cited by 125 · see citing works
Molecular mechanisms of curcumin and its analogs in colon cancer prevention and treatment
Selvam, C., Prabu, S. L., Jordan, B. C., Purushothaman, Y., Umamaheswari, A., Hosseini‐Zare, M. S., & Thilagavathi, R. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.117032 · Cited by 125 · see citing works
EGFR and KRAS in Colorectal Cancer
Markman, B., Ramos, F. J., Capdevila, J., & Tabernero, J. M. (2010) · Advances in clinical chemistry · doi:10.1016/s0065-2423(10)51004-7 · Cited by 126 · see citing works
Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways
Katz, D., Lazar, A. J., & Lev, D. C. (2009) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399409001227 · Cited by 124 · see citing works
Targeted therapies for targeted populations: Anti-EGFR treatment for EGFR amplified gastroesophageal adenocarcinoma
Maron, S., Alpert, L., Kwak, H., Lomnicki, S., Chase, L. M., Xu, D., O’Day, E., Nagy, R., Lanman, R., Cecchi, F., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1260 · Cited by 116 · see citing works
“HER2, n (%) Positive 2 (25) 29 (22) 1 Negative 6 (75) 90 (68) Equivocal 0 (0) 2 (2) Unknown 0 (0) 11 (8)”
Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer
Sforza, V., Martinelli, E., Ciardiello, F., Gambardella, V., Napolitano, S., Martini, G., della Corte, C., Cardone, C., Ferrara, M. L., Reginelli, A., et al. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i28.6345 · Cited by 123 · see citing works
The Role of KRAS Mutation Testing in the Management of Patients With Metastatic Colorectal Cancer
Monzon, F. A., Ogino, S., Hammond, M. E., Halling, K. C., Bloom, K. J., & Nikiforova, M. N. (2009) · Archives of Pathology & Laboratory Medicine · doi:10.5858/133.10.1600 · Cited by 123 · see citing works
Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant
Molinari, F., Martin, V, Saletti, P., De Dosso, S., Spitale, A., Camponovo, A., Bordoni, A., Crippa, S., Mazzucchelli, L., & Frattini, M. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604848 · Cited by 122 · see citing works
“Second, besides the expected occurrence of G12D mutation (Frattini et al, 2007), we observed an unusual high frequency of G12A mutations, suggesting that this type of K-Ras alteration may confer a higher aggressive phenotype.”
BackgroundMethodResultInfluentialSelf-citation
The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic target
Shalaby, A. A., Presneau, N., Ye, H., Halai, D., Berisha, F., Idowu, B. D., Leithner, A., Liegl, B., Briggs, T. W. R., Bácsi, K., et al. (2010) · The Journal of Pathology · doi:10.1002/path.2818 · Cited by 118 · see citing works
Oncogenic mutations as predictive factors in colorectal cancer
Lièvre, A., Blons, H., & Laurent-Puig, P. (2010) · Oncogene · doi:10.1038/onc.2010.89 · Cited by 117 · see citing works
“The loss of PTEN protein expression (30% of colorectal tumours) may therefore be an additional factor of PI3K/AKT pathway activation, which may be responsible for resistance to anti-EGFR antibodies, as it was firstly reported in a small series of 27 patients in which PTEN protein expression was evaluated by immunohist…”
BackgroundMethodInfluential
A Multicenter Blinded Study to Evaluate KRAS Mutation Testing Methodologies in the Clinical Setting
Whitehall, V., Tran, K. L., Umapathy, A., Grieu, F., Hewitt, C., Evans, T., Ismail, T., Li, W. Q., Collins, P., Ravetto, P. F., et al. (2009) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2009.090057 · Cited by 113 · see citing works
EGFR mutations and the terminal respiratory unit
Yatabe, Y. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9205-8 · Cited by 112 · see citing works
Targeted therapies: how personal should we go?
Martini, M., Vecchione, L., Siena, S., Tejpar, S., & Bardelli, A. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.164 · Cited by 111 · see citing works
Targeted therapy for hepatocellular carcinoma
Spangenberg, H. C., Thimme, R., & Blum, H. E. (2009) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.86 · Cited by 112 · see citing works
Tumour suppressor genes in chemotherapeutic drug response
Lai, D., Grieve, S., & Yang, X. (2012) · Bioscience Reports · doi:10.1042/bsr20110125 · Cited by 109 · see citing works
KRAS Mutation Testing in Colorectal Cancer
Plesec, T. P., & Hunt, J. L. (2009) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e3181a9d4ed · Cited by 107 · see citing works
EGFR-targeted therapy
Vecchione, L., Jacobs, B., Normanno, N., Ciardiello, F., & Tejpar, S. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.08.021 · Cited by 107 · see citing works
Present and future of metastatic colorectal cancer treatment: A review of new candidate targets
Martini, G., Troiani, T., Cardone, C., Vitiello, P. P., Sforza, V., Ciardiello, D., Napolitano, S., Corte, C. M. D., Morgillo, F., Raucci, A., et al. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i26.4675 · Cited by 105 · see citing works
Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?
Rizzo, S., Bronte, G., Fanale, D., Corsini, L. R., Silvestris, N., Santini, D., Gulotta, G., Bazan, V., Gebbia, N., Fulfaro, F., et al. (2010) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(10)70021-9 · Cited by 163 · see citing works
Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy
Manceau, G., Imbeaud, S., Thiébaut, R., Liébaert, F., Fontaine, K., Rousseau, F., Génin, B., Corre, D. L., Didelot, A., Vincent, M., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2750 · Cited by 103 · see citing works
Targeted therapy for triple‐negative breast cancer: Where are we?
Duffy, M. J., McGowan, P. M., & Crown, J. P. (2012) · International Journal of Cancer · doi:10.1002/ijc.27632 · Cited by 102 · see citing works
KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer
Mao, C., Huang, Y., Yang, Z., Zheng, D., Chen, J., & Tang, J. (2012) · Cancer · doi:10.1002/cncr.27804 · Cited by 98 · see citing works
“Moroni 2005(13) Italy 21 72 [41-85] 17 (81) 12 (57) 11 (52) 1 (5) 4 (19) 16(76) DS RECIST Lievre 2006(6) France 30 62 [41-78] 19 (63) 1 (3) 3 (10) 3 (10) 10 (33) 17(57) DS RECIST Benvenuti 2007(18) Italy 22 68 [39-84] 17 (77) 12 (55) 11 (50) 1 (5) 4 (18) 17(77) DS RECIST Frattini 2007(14) Switzerland 27 67 [29-84] 18…”
PTEN Gene Expression and Mutations in the PIK3CA Gene as Predictors of Clinical Benefit to Anti-Epidermal Growth Factor Receptor Antibody Therapy in Patients With KRAS Wild-Type Metastatic Colorectal Cancer
Sood, A., McClain, D., Maitra, R., Basu-Mallick, A., Seetharam, R. N., Kaubisch, A., Rajdev, L. N., Mariadason, J. M., Tanaka, K. E., & Goel, S. (2012) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2011.12.001 · Cited by 98 · see citing works
“This identification of PTEN/ PIK3CA status as a putative biomarker is consistent with prior reports [24, 26–29, 53–55].”
Result
Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash
Schilder, R. J., Pathak, H. B., Lokshin, A. E., Holloway, R. W., Alvarez, R. D., Aghajanian, C. A., Min, H., Devarajan, K., Ross, E. A., Drescher, C. W., et al. (2009) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.12.003 · Cited by 98 · see citing works
EGFR in melanoma: clinical significance and potential therapeutic target
Boone, B., Jacobs, K., Ferdinande, L., Taildeman, J., Lambert, J., Peeters, M., Bracke, M., Pauwels, P., & Brochez, L. (2011) · Journal of Cutaneous Pathology · doi:10.1111/j.1600-0560.2011.01673.x · Cited by 97 · see citing works
Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: Beyond KRAS mutations
Custodio, A., & Feliú, J. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2012.05.001 · Cited by 96 · see citing works
“[43] Frattini M, Saletti P, Romagnani E, et al.”
BackgroundInfluential
Rechallenge therapy and treatment holiday: different strategies in management of metastatic colorectal cancer
Tonini, G., Imperatori, M., Vincenzi, B., Frezza, A. M., & Santini, D. (2013) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-32-92 · Cited by 96 · see citing works
“However, the overall response rate (ORR) to cetuximab or panitumumab based regimens is less than 30%, suggesting that primary resistance mechanisms are present in many cases [6-19].”
Background
Cetuximab-Based Immunotherapy and Radioimmunotherapy of Head and Neck Squamous Cell Carcinoma
Niu, G., Sun, X., Cao, Q., Courter, D. L., Koong, A. C., Le, Q., Gambhir, S. S., & Chen, X. S. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2495 · Cited by 95 · see citing works
“KRAS mutation and PTEN loss have also been reported to be related to the resistance of colorectal cancers to cetuximab treatment (33, 34).”
Background
Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: A meta-analysis of 22 studies
Qiu, L., Mao, C., Zhang, J., Zhu, X.-D., Liao, R.-Y., Xue, K., Li, J., & Chen, Q. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.05.022 · Cited by 93 · see citing works
Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence
Troiani, T., Napolitano, S., Della Corte, C. M., Martini, G., Martinelli, E., Morgillo, F., & Ciardiello, F. (2016) · ESMO Open · doi:10.1136/esmoopen-2016-000088 · Cited by 104 · see citing works
Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study
Razis, E. D., Briasoulis, E. C., Vrettou, E., Skarlos, D. V., Papamichael, D., Kostopoulos, I. S., Samantas, E., Xanthakis, I., Bobos, M., Galanidi, E., et al. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-234 · Cited by 90 · see citing works
“More importantly, the recently published report by Frattini et al [10] also examined PTEN by IHC and discovered a correlation between loss of PTEN protein expression and lack of response to cetuximab.”
BackgroundInfluential

EGFR gene gain and PTEN protein expression are favorable prognostic factors in patients with KRAS wild-type metastatic colorectal cancer treated with cetuximab
Razis, E. D., Pentheroudakis, G. E., Rigakos, G., Bobos, M., Kouvatseas, G., Tzaida, O., Makatsoris, T., Papakostas, P., Bai, M. C., GOUSSIA, A. C., et al. (2014) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-014-1626-2 · Cited by 34 · see citing works
Analysis of epidermal growth factor receptor (EGFR) downstream proteins in metastatic colorectal cancer patients: Comparison between primary tumor and related metastatic sites
Saletti, P., Molinari, F., Martín, V., Bordoni, A., Crippa, S., Mazzucchelli, L., & Frattini, M. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.11075 · Cited by 3 · see citing works
Self-citation
Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study
Razis, E. D., Briasoulis, E. C., Vrettou, E., Skarlos, D. V., Papamichael, D., Kostopoulos, I. S., Samantas, E., Xanthakis, I., Bobos, M., Galanidi, E., et al. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-234 · Cited by 90 · see citing works
Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer
Laurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6796 · Cited by 673 · see citing works
Pten expression and Kras mutations as predictors of benefit from cetuximab plus irinotecan (CETIRI) in metastatic colorectal cancer (MCRC) patients (PTS)
Loupakis, F., Stasi, I., Pollina, L., Ruzzo, A., Masi, G., Cremolini, C., Funel, N., Fornaro, L., Baldi, G. G., Salvatore, L., et al. (2008) · CINECA IRIS Institutial research information system (University of Pisa) · doi:10.1093/annonc/mdn616

Authors: Frattini, M., Saletti, P., Romagnani, E., Martin, V, Molinari, F., Ghisletta, M., Camponovo, A., Etienne, L. L., Cavalli, F., & Mazzucchelli, L.
Affiliations: Istituto Cantonale di Patologia (CH)
Ospedale San Giovanni Bellinzona (CH)
Corresponding author: Frattini, M
ORCID: Frattini, M
Cavalli, F
Venue: British Journal of Cancer
Publisher: Springer Science and Business Media LLC
Published: 2007-10
Volume: 97
Issue: 8
Pages: 1139-1145
ISSN: 0007-0920 (ISSN-L)
1532-1827
DOI: 10.1038/sj.bjc.6604009
PMC: PMC2360431
OpenAlex: W2100589633
Cited by: 540
References: 31
Citations by year: 2026: 3 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 9 · 2017: 15 · 2016: 20 · 2015: 30 · 2014: 38 · 2013: 38 · 2012: 63
FWCI: 33.57
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
www.springer.com/tdm (unspecified)
Locations: British Journal of Cancer (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Oncosuisse
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords: PTEN loss, cetuximab, metastatic colorectal cancer, EGFR overexpression, EGFR amplification, KRAS mutation, chromosome 7 polysomy, drug response prediction, predictive biomarkers
MeSH terms: Cetuximab, Adult, Aged, Algorithms, Antibodies, Monoclonal, Antineoplastic Agents, Chromosomes, Human, Pair 7, Female, Gene Amplification, Humans, Immunohistochemistry, Male, Middle Aged, Proto-Oncogene Proteins, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression, Proto-Oncogene Proteins p21(ras), In Situ Hybridization, Fluorescence, ras Proteins, Drug Resistance, Neoplasm, PTEN Phosphohydrolase, 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

PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks