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

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

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

DOI 10.1038/sj.bjc.6604009PMC PMC2360431

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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.

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Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis
Tabibzadeh, A., Tameshkel, F. S., Moradi, Y., Soltani, S., Moradi‐Lakeh, M., Ashrafi, G. H., Motamed, N., Zamani, F., Motevalian, S. A., Panahi, M., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-73770-1 · Cited by 29
Artificial Intelligence–Assisted Amphiregulin and Epiregulin IHC Predicts Panitumumab Benefit in RAS Wild-Type Metastatic Colorectal Cancer
Williams, C. J. M., Seligmann, J. F., Elliott, F., Shires, M., Richman, S. D., Brown, S., Zhang, L., Singh, S., Pugh, J., Xu, X.-M., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0120 · Cited by 26
“Consequently, RAS - (24), BRAF - (25), and PIK3CA -mutation status (26), and PTEN protein expression (27) have all been examined as potential predictive biomarkers for anti-EGFR therapy bene ﬁ t, as have EGFR (28), HER2 (29), and HER3 (30) ampli ﬁ cation and mutation, and EGFR gene copy number (31).”
Background
PHLDB2 Mediates Cetuximab Resistance via Interacting With EGFR in Latent Metastasis of Colorectal Cancer
Luo, M., Huang, Z., Yang, X., Chen, Y., Jiang, J., Zhang, L., Zhou, L., Qin, S., Jin, P., Fu, S., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.12.011 · Cited by 28
“As the direct target of cetuximab, EGFR expression has been proposed as a potential marker of clinical efficacy in early trials with cetuximab.(39) However, the correlation between EGFR expression and cetuximab response is not evident in CRC,(14,40,41) and the underlying mechanism that mediates resistance to EGFR-targ…”
Background
Pre-trial inter-laboratory analytical validation of the FOCUS4 personalised therapy trial
Richman, S. D., Adams, R., Quirke, P., Butler, R., Hemmings, G., Chambers, P. A., Roberts, H. C., James, M. D., Wozniak, S., Bathia, R., et al. (2015) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2015-203097 · Cited by 27
Prognostic Value of BRAF, PI3K, PTEN, EGFR Copy Number, Amphiregulin and Epiregulin Status in Patients with KRAS Codon 12 Wild-Type Metastatic Colorectal Cancer Receiving First-Line Chemotherapy with Anti-EGFR Therapy
Llovet, P., Sastre, J., Sanz‐Ortega, J., Bando, I., Ferrer, M., Alfonso, P. G., Donnay, O., Carrato, A., Jiménez, A., Aranda, E., et al. (2015) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-015-0165-0 · Cited by 28
“Some data have suggested that loss of PTEN expression measured by immunohistochemistry may predict resistance to anti-EGFR therapy in patients with mCRC [21, 24, 29, 36, 39, 47]; nevertheless, other studies, including ours, are negative [27, 36].”
Result
The role of anti-epidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer
Bouché, O., Beretta, G. D., Alfonso, P., & Geißler, M. (2010) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(10)00036-8 · Cited by 27
Cetuximab-based therapy for metastatic colorectal cancer: a meta-analysis of the effect of K-ras mutations
Ibrahim, E. M., Zekri, J., & Sadiq, B. M. B. (2010) · International Journal of Colorectal Disease · doi:10.1007/s00384-010-0927-4 · Cited by 27
“Other studies linked response to anti-EGFR therapy to BRAF status [35], loss of PTEN protein expression [20], and EGFR copy number [12, 18, 36].”
BackgroundMethod
Molecular characterization and biomarker identification in colorectal cancer: Toward realization of the precision medicine dream
Goel, G. (2018) · Cancer Management and Research · doi:10.2147/cmar.s162967 · Cited by 26
Strategies to overcome resistance to epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer
Jeong, W.-J. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i29.9862 · Cited by 26
Predictive Molecular Classifiers in Colorectal Cancer
Bohanes, P. O., LaBonte, M. J., Winder, T., & Lenz, H. (2011) · Seminars in Oncology · doi:10.1053/j.seminoncol.2011.05.012 · Cited by 26
Chasing the personalized medicine dream through biomarker validation in colorectal cancer
Patil, H., Saxena, S. G., Barrow, C. J., Kanwar, J. R., Kapat, A., & Kanwar, R. K. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.09.022 · Cited by 25
Genetic Polymorphisms of FcγRIIa and FcγRIIIa Are Not Predictive of Clinical Outcomes after Cetuximab plus Irinotecan Chemotherapy in Patients with Metastatic Colorectal Cancer
Park, S., Hong, Y. S., Lee, J., Ryu, M., Chang, H. M., Kim, K., Ahn, Y., Na, Y.-S., Jin, D., Yu, C. S., et al. (2012) · Oncology · doi:10.1159/000335959 · Cited by 25
Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer
Bohn, B. A., Mina, S., Krohn, A., Simon, R., Kluth, M., Harasimowicz, S., Quaas, A., Bockhorn, M., Izbicki, J. R., Sauter, G., et al. (2013) · Human Pathology · doi:10.1016/j.humpath.2012.12.006 · Cited by 25
“These studies show highly discordant results, with PTEN loss rates ranging from 5% up to 66% [8,14,16-18,23-34].”
Result
Relationship Between Colorectal Cancer Biomarkers and Response to Epidermal Growth Factor Receptor Monoclonal Antibodies
Hawkes, E. A., & Cunningham, D. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.29.5626 · Cited by 25
Integrating anti-EGFR therapies in metastatic colorectal cancer.
Haraldsdóttir, S., & Bekaii‐Saab, T. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2078-6891.2013.028 · Cited by 24
“PIK3CA mutations and/or PTEN loss have been shown to predict response in some (70-73) but not all studies (74,75).”
Background
Clinical Benefit of High-Sensitivity KRAS Mutation Testing in Metastatic Colorectal Cancer Treated with Anti-EGFR Antibody Therapy
Kimura, T., Okamoto, K., Miyamoto, H., Kimura, M., Kitamura, S., Takenaka, H., Muguruma, N., Okahisa, T., Aoyagi, E., Kajimoto, M., et al. (2012) · Oncology · doi:10.1159/000336792 · Cited by 24
Guidelines for biomarker testing in colorectal carcinoma (CRC): a national consensus of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM)
Alfonso, P. G., Salazar, R., García‐Foncillas, J., Musulén, E., García‐Carbonero, R., Payá, A., Pérez‐Segura, P., y Cajal, S. R., & Navarro, S. (2012) · Clinical & Translational Oncology · doi:10.1007/s12094-012-0856-5 · Cited by 25
“correlated with failure to respond to cetuximab [60–62].”
Background
Panitumumab in Combination With Cytotoxic Chemotherapy for the Treatment of Metastatic Colorectal Carcinoma
Peeters, M., Cohn, A. L., Köhne, C., & Douillard, J. (2011) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2011.06.010 · Cited by 24
Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options
Rodrigues, D., Longatto‐Filho, A., & Martins, S. F. F. (2016) · BioMed Research International · doi:10.1155/2016/6896024 · Cited by 24
Precision Oncology—The Quest for Evidence
Soldatos, T. G., Kaduthanam, S., & Jackson, D. (2019) · Journal of Personalized Medicine · doi:10.3390/jpm9030043 · Cited by 24
“(R10): Down-regulation of a tumor suppressor leading to activation of downstream signaling [20,21].”
Impact ofKRASmutation and PTEN expression on cetuximab-treated colorectal cancer
Li, F. H. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i46.5881 · Cited by 24
Sprouty2 protein enhances the response to gefitinib through epidermal growth factor receptor in colon cancer cells
Feng, Y., Tsao, C., Wu, C., Chang, J., Lu, P., Yeh, K., Shieh, G.-S., Shiau, A., & Lee, J.-C. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01637.x · Cited by 24
KRAS Mutation Screening in Colorectal Cancer: From Paper to Practice
Fakih, M. (2010) · Clinical Colorectal Cancer · doi:10.3816/ccc.2010.n.003 · Cited by 24
Screening for EGFR Mutations in Patients with Head and Neck Cancer Treated with Gefitinib on a Compassionate-Use Program: A Hellenic Cooperative Oncology Group Study
Murray, S. J., Bobos, M., Angouridakis, N., Nikolaou, A. C., Linardou, H., Razis, E. D., & Fountzilas, G. (2010) · Journal of Oncology · doi:10.1155/2010/709678 · Cited by 24
Current Development of Monoclonal Antibodies in Cancer Therapy
Parakh, S., King, D., Gan, H. K., & Scott, A. M. (2019) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-030-23765-3_1 · Cited by 25
P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab
Bouali, S., Chrétien, A.-S., Ramacci, C., Rouyer, M., Marchal, S., Galenne, T., Juin, P. P., Bécuwe, P., & Merlin, J. (2009) · Cancer Gene Therapy · doi:10.1038/cgt.2008.100 · Cited by 24
Phosphatase and tensin homolog expression related to cetuximab effects in colorectal cancer patients: A meta-analysis
Shen, Y. L. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i21.2712 · Cited by 24
Proteins of the VEGFR and EGFR pathway as predictive markers for adjuvant treatment in patients with stage II/III colorectal cancer: results of the FOGT-4 trial
Thomaidis, T., Maderer, A., Formentini, A., Bauer, S. L., Trautmann, M., Schwarz, M., Neumann, W., Kittner, J. M., Schad, A., Link, K.-H., et al. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-014-0083-8 · Cited by 23
“Inactivation or loss of PTEN protein expression is found in up to 30% of sporadic CRC [30,31] and is likely to be associated with resistance to anti-EGFR monoclonal antibodies in KRASwt patients [32].”
Background
Role of cetuximab and sorafenib in treatment of metastatic colorectal cancer
Galal, K., Khaled, Z., & Mourad, A. M. M. (2011) · Indian Journal of Cancer · doi:10.4103/0019-509x.75825 · Cited by 23
Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer
Bai, B., Shan, L., Xie, B., Huang, X., Mao, W., Wang, X., Wang, D., & Zhu, H. (2017) · Oncology Letters · doi:10.3892/ol.2017.7709 · Cited by 23
“G12D in the present study was the most prominent subtype which was congruent with data from Caucasian and other Chinese mCRC (25-27).”
A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer
Goodwin, R. A., Jonker, D. J., Chen, E. X., Kennecke, H. F., Cabanero, M., Tsao, M., Vickers, M. M., Bohemier, C., Lim, H. J., Ritter, H. D., et al. (2019) · Investigational New Drugs · doi:10.1007/s10637-019-00814-3 · Cited by 23
Effect of mTOR Inhibitors in Nude Mice with Endometrial Carcinoma and Variable PTEN Expression Status
Fong, P., & Meng, L. (2014) · Medical science monitor basic research/Medical science monitor. Basic research · doi:10.12659/msmbr.892514 · Cited by 22
“The loss of PTEN expression was also associated with non-responsiveness to treatment with cetuximab in metastatic colorectal cancer patients, and the authors of the study suggested that PTEN expression may predict the efficacy of certain drug treatments for colorectal cancer [43].”
Background
Biomarkers for predicting the outcome of various cancer immunotherapies
Jafarzadeh, L., Khakpoor-Koosheh, M., Mirzaei, H., & Mirzaei, H. R. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.103161 · Cited by 21
Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment
Hasbal‐Celikok, G., Aksoy-Sagirli, P., Ülbegi, G. A., & Can, A. (2021) · Oncology Letters · doi:10.3892/ol.2021.12470 · Cited by 23
mCOPA: analysis of heterogeneous features in cancer expression data
Wang, C., Taciroglu, A., Maetschke, S., Nelson, C. C., Ragan, M. A., & Davis, M. J. (2012) · Journal of Clinical Bioinformatics · doi:10.1186/2043-9113-2-22 · Cited by 22
“PTEN is a known tumour suppressor, and loss of PTEN function is associated with cancer progression [51,52].”
Background
Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells
Garay, T., Kenessey, I., Molnár, E., Juhász, É., Réti, A., László, V., Rózsás, A., Dobos, J., Döme, B., Berger, W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117021 · Cited by 22
“Interestingly, PTEN loss conferred resistance against EGFR inhibitors in colorectal and lung cancer [62, 63], against herceptin in breast cancer [64] or even BRAF inhibitors in melanoma [65].”
Background
Proteomic characterization of the colorectal cancer response to chemoradiation and targeted therapies reveals potential therapeutic strategies
Li, Y., Wang, B., Ma, F., Jiang, D., Wang, Y., Li, K., Tan, S., Feng, J., Wang, Y., Qin, Z., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101311 · Cited by 23
Personalized treatment for advanced colorectal cancer: KRAS and beyond
Karapetis, C. S., & Patel, G. S. (2013) · Cancer Management and Research · doi:10.2147/cmar.s35025 · Cited by 20
Personalizing Colon Cancer Therapeutics: Targeting Old and New Mechanisms of Action
Kline, C., & El‐Deiry, W. S. (2013) · Pharmaceuticals · doi:10.3390/ph6080988 · Cited by 24
“Majority of patients that have a dramatic reduction/loss of PTEN expression in their tumors do not respond to cetuximab [244,245].”
Background
Overview of biomarkers in metastatic colorectal cancer: Tumour, blood and patient-related factors
Clarke, S. J., Karapetis, C. S., Gibbs, P., Pavlakis, N., Desai, J., Michael, M., Tebbutt, N. C., Price, T. J., & Tabernero, J. M. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2012.06.001 · Cited by 21
“Several tudies have suggested that PIK3CA mutations and/or PTEN oss may be associated with resistance to EGFR mAb therpy [53,54,57,58].”
Background
Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review
Merla, A., & Goel, S. (2012) · Chemotherapy Research and Practice · doi:10.1155/2012/387172 · Cited by 22
“Since then, several clinical studies have been reported, with conflicting results; with some reports suggesting a predictive role of this pathway and others refuting this finding [11, 89–96].”
Result
Well-Differentiated Follicular Patterned Tumors of the Thyroid With High-Grade Features Can Metastasize in the Absence of Capsular or Vascular Invasion
Bongiovanni, M., Mazzucchelli, L., Giovanella, L., Frattini, M., & Pusztaszeri, M. P. (2014) · International Journal of Surgical Pathology · doi:10.1177/1066896914531814 · Cited by 21
Self-citation
Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity
Takata, M., Chikumi, H., Miyake, N., Adachi, K., Kanamori, Y., Yamasaki, A., Igishi, T., Burioka, N., Nanba, E., & Shimizu, E. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.19238 · Cited by 21
Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience
Bongiovanni, M., Molinari, F., Eszlinger, M., Paschke, R., Barizzi, J., Merlo, E., Giovanella, L., Fasolini, F., Cattaneo, F., Ramelli, F., et al. (2014) · Cytopathology · doi:10.1111/cyt.12226 · Cited by 21
Self-citation
Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer
Phua, L. C., Ng, H. W., Yeo, A. H. L., Chen, E., Lo, M., Cheah, P. Y., Chan, E. C. Y., Koh, P. K., & Ho, H. K. (2015) · Oncology Letters · doi:10.3892/ol.2015.3560 · Cited by 21
Cellular response to cetuximab in PTEN-silenced head and neck squamous cell carcinoma cell line
Faivre (2010) · International Journal of Oncology · doi:10.3892/ijo_00000809 · Cited by 21
Treatment Individualization in Colorectal Cancer
van Geel, R. M. J. M., Beijnen, J. H., Bernards, R., & Schellens, J. H. M. (2015) · Current Colorectal Cancer Reports · doi:10.1007/s11888-015-0288-z · Cited by 20
Changing Pathology with Changing Drugs: Tumors of the Gastrointestinal Tract
Cervera, P., & Fléjou, J. (2011) · Pathobiology · doi:10.1159/000315535 · Cited by 23
PTEN deletion potentiates invasion of colorectal cancer spheroidal cells through 3D Matrigel
Chandrasekaran, S., Deng, H., & Ye, F. (2015) · Integrative Biology · doi:10.1039/c4ib00298a · Cited by 21
A novel AMPK activator reduces glucose uptake and inhibits tumor progression in a mouse xenograft model of colorectal cancer
Valtorta, S., Nicolini, G., Tripodi, F., Meregalli, C., Cavaletti, G., Avezza, F., Crippa, L., Bertoli, G. R., Sanvito, F., Fusi, P. A., et al. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0148-8 · Cited by 20
“The efficacy of the most promising EGFR-targeted therapies, such as cetuximab and panitumumab, is often hampered by the presence of K-Ras mutations and other alterations occurring in EGFR downstream pathways (BRAF and PIK3CA mutation, and PTEN loss of expression), leading to drug resistance [8, 9].”
Background
PTEN plasticity: how the taming of a lethal gene can go too far
Naguib, A., & Trotman, L. C. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.03.003 · Cited by 21
Pharmacogenetic screening for drug therapy: From single gene markers to decision making in the next generation sequencing era
Tzvetkov, M. V., & von Ahsen, N. (2012) · Pathology · doi:10.1097/pat.0b013e32834f4d69 · Cited by 20
Activation of signal pathways and the resistance to anti‐EGFR treatment in colorectal cancer
Chen, J., Huang, X., & Katsifis, A. G. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22905 · Cited by 19
“In CRC patients treated with cetuximab, PTEN as identified by FISH has been negatively correlated with response to treatment [Frattini et al., 2007; Laurent-Puig et al., 2009; Loupakis et al., 2009; Negri et al., 2010].”
Method

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

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

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