Cited by 1,858HER2/EGFR in Cancer ResearchPI3K/AKT/mTOR signaling in cancerBreast Cancer Treatment Studies

The DOI matches its Crossref record; 65 of the 70 references it cites were found in a registry or an index.

PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients

Open access

Nagata, Yoichi, Lan, Keng-Hsueh, Zhou, Xiaoyan, Tan, Ming, Esteva, Francisco J., Sahin, Aysegul A., Klos, Kristine S., Li, Ping, Monia, Brett P., Nguyen, Nina T., Hortobagyi, Gabriel N., Hung, Mien-Chie, Yu, Dihua·2004·Cancer Cell

DOI 10.1016/j.ccr.2004.06.022

Open this paper in CoChat — free account Open PDF

Abstract

The ErbB2-targeting antibody, trastuzumab (Herceptin), has remarkable therapeutic efficacy in certain patients with ErbB2-overexpressing tumors. The overall trastuzumab response rate, however, is limited and what determines trastuzumab response is poorly understood. Here we report that PTEN activation contributes to trastuzumab's antitumor activity. Trastuzumab treatment quickly increased PTEN membrane localization and phosphatase activity by reducing PTEN tyrosine phosphorylation via Src inhibition. Reducing PTEN in breast cancer cells by antisense oligonucleotides conferred trastuzumab resistance in vitro and in vivo. Patients with PTEN-deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. Thus, PTEN deficiency is a powerful predictor for trastuzumab resistance. Additionally, PI3K inhibitors rescued PTEN loss-induced trastuzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance.

Integrity signals

Registry

Crossref · 10.1016/j.ccr.2004.06.022

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu Oncogene
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., & McGuire, W. L. (1987) · Science · doi:10.1126/science.3798106 · Cited by 11,760
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2
Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103153441101 · Cited by 11,500
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Cobleigh, M., Vogel, C. L., Tripathy, D., Robert, N. J., Scholl, S., Fehrenbacher, L., Wolter, J. M., Paton, V. E., Shak, S., Lieberman, G., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.9.2639 · Cited by 2,767
New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
Cantley, L. C., & Neel, B. G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4240 · Cited by 2,018
Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer
Vogel, C. L., Cobleigh, M. A., Tripathy, D., Gutheil, J. C., Harris, L. N., Fehrenbacher, L., Slamon, D. J., Murphy, M., Novotny, W. F., Burchmore, M., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.3.719 · Cited by 1,860
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab
Cho, H., Mason, K., Ramyar, K. X., Stanley, A. M., Gabelli, S. B., Denney, D. W., & Leahy, D. J. (2003) · Nature · doi:10.1038/nature01392 · Cited by 1,637
The Multiple Roles of PTEN in Tumor Suppression
Di Cristofano, A., & Pandolfi, P. P. (2000) · Cell · doi:10.1016/s0092-8674(00)80674-1 · Cited by 1,182
Insulin-Like Growth Factor-I Receptor Signaling and Resistance to Trastuzumab (Herceptin)
Lu, Y., Zi, X., Zhao, Y., Mascarenhas, D. D., & Pollak, M. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.24.1852 · Cited by 886

Flagged first, then by citations

Show all 70 references

5 of the 70 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

Petit, 1997, Neutralizing antibodies against epidermal growth factor and ErbB2/neu receptor tyrosine kinase down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo, Am. J. Pathol., 151, 1523

Sorted by citations

Items 201–300 of 1,001

Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma
Maadi, H., Soheilifar, M. H., Choi, W.-S., Moshtaghian, A., & Wang, Z. (2021) · Cancers · doi:10.3390/cancers13143540 · Cited by 191
The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer
Castañeda, C. A., Cortés-Funes, H., Gómez, H., & Ciruelos, E. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9261-0 · Cited by 173
Circulating tumour cells and cell-free DNA as tools for managing breast cancer
Mattos‐Arruda, L. D., Cortés, J., Santarpia, L., Vivancos, A. P., Tabernero, J. M., Reis-Filho, J. S., & Seoane, J. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.80 · Cited by 176
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 177
Antitumor Activity of NVP-BKM120—A Selective Pan Class I PI3 Kinase Inhibitor Showed Differential Forms of Cell Death Based on p53 Status of Glioma Cells
Koul, D., Fu, J., Shen, R., LaFortune, T. A., Wang, S., Tiao, N., Kim, Y., Liu, J.-L., Ramnarian, D., Yuan, Y., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1558 · Cited by 172
Monoclonal antibodies for the treatment of cancer
Shuptrine, C. W., Surana, R., & Weiner, L. M. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.12.009 · Cited by 177
Epidermal Growth Factor Receptor (EGFR) Ubiquitination as a Mechanism of Acquired Resistance Escaping Treatment by the Anti-EGFR Monoclonal Antibody Cetuximab
Lu, Y., Li, X., Liang, K., Luwor, R., Siddik, Z. H., Mills, G. B., Mendelsohn, J., & Fan, Z. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0589 · Cited by 170
Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors
Steelman, L. S., Navolanic, P. M., Sokolosky, M. L., Taylor, J. R., Lehmann, B. D., Chappell, W. H., Abrams, S. L., Wong, E. W. T., Stadelman, K. M., Terrian, D. M., et al. (2008) · Oncogene · doi:10.1038/onc.2008.49 · Cited by 170
Molecular predictors of response to trastuzumab and lapatinib in breast cancer
Esteva, F. J., Yu, D., Hung, M., & Hortobágyi, G. N. (2009) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.216 · Cited by 170
The Protein Phosphatase Activity of PTEN Regulates Src Family Kinases and Controls Glioma Migration
Dey, N., Crosswell, H. E., De, P. K. R., Parsons, R. E., Peng, Q., Su, J. D., & Durden, D. L. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-1182 · Cited by 168
PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
Duan, S., Yuan, G., Liu, X., Ren, R., Li, J., Zhang, W., Wu, J., Xu, X., Fu, L., Li, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms10068 · Cited by 172
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
Pertuzumab: new hope for patients with HER2-positive breast cancer
Capelán, M., Pugliano, L., de Azambuja, E., Bozovic, I., Saini, K. S., Sotiriou, C. P., Loi, S., & Piccart, M. J. (2012) · Annals of Oncology · doi:10.1093/annonc/mds328 · Cited by 174
Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3
André, F., Hurvitz, S. A., Fasolo, A., Tseng, L., Jérusalem, G., Wilks, S. T., O'Regan, R. M., Isaacs, C. J., Toi, M., Burris, H. A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.9161 · Cited by 167
Transforming Growth Factor β Engages TACE and ErbB3 To Activate Phosphatidylinositol-3 Kinase/Akt in ErbB2-Overexpressing Breast Cancer and Desensitizes Cells to Trastuzumab
Wang, S. E., Xiang, B., Guix, M., Olivares, M. G., Parker, J. S., Chung, C. H., Pandiella, A., & Arteaga, C. L. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00787-08 · Cited by 168
EGFR, HER2 and VEGF Pathways
Press, M. F., & Lenz, H. (2007) · Drugs · doi:10.2165/00003495-200767140-00006 · Cited by 172
Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer
Canonici, A., Gijsen, M., Mullooly, M., Bennett, R., Bouguern, N., Pedersen, K., O’Brien, N. A., Roxanis, I., Li, J., Bridge, E., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1148 · Cited by 164
Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens
Blackwell, K., Pegram, M. D., Tan-Chiu, E., Schwartzberg, L. S., Arbushites, M. C., Maltzman, J., Forster, J. K., Rubin, S. D., Stein, S. H., & Burstein, H. J. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn759 · Cited by 164
Mechanisms of Acquired Resistance to Targeted Cancer Therapies
Lackner, M. R., Wilson, T. R., & Settleman, J. (2012) · Future Oncology · doi:10.2217/fon.12.86 · Cited by 167
miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer
Epis, M. R., Giles, K. M., Barker, A. J., Kendrick, T. S., & Leedman, P. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.030098 · Cited by 164
In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer
Janiszewska, M., Liu, L., Almendro, V., Kuang, Y., Paweletz, C. P., Sakr, R. A., Weigelt, B., Hanker, A. B., Chandarlapaty, S., King, T. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3391 · Cited by 163
Regulation of PTEN Activity by Its Carboxyl-terminal Autoinhibitory Domain
Odriozola, L., Singh, G., Hoang, T., & Chan, A. M.-L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611240200 · Cited by 160
Status of PI3K inhibition and biomarker development in cancer therapeutics
Markman, B., Atzori, F., Pérez-García, J. M., Tabernero, J. M., & Baselga, J. M. (2009) · Annals of Oncology · doi:10.1093/annonc/mdp347 · Cited by 160
Systems Biology Reveals New Strategies for Personalizing Cancer Medicine and Confirms the Role of PTEN in Resistance to Trastuzumab
Faratian, D., Goltsov, A., Lebedeva, G., Sorokin, A., Moodie, S., Mullen, P., Kay, C., Um, I. H., Langdon, S. P., Goryanin, I., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0777 · Cited by 158
Polyvalent Folate-Dendrimer-Coated Iron Oxide Theranostic Nanoparticles for Simultaneous Magnetic Resonance Imaging and Precise Cancer Cell Targeting
Luong, D., Sau, S., Kesharwani, P., & Iyer, A. K. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.6b01885 · Cited by 159
Biomarkers of Response to Akt Inhibitor MK-2206 in Breast Cancer
Sangai, T., Akçakanat, A., Chen, H., Tarco, E., Wu, Y., Do, K.-A., Miller, T. W., Arteaga, C. L., Mills, G. B., Gonzalez-Angulo, A. M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1141 · Cited by 158
Dual mTORC1/2 and HER2 Blockade Results in Antitumor Activity in Preclinical Models of Breast Cancer Resistant to Anti-HER2 Therapy
García-García, C., Ibrahim, Y. H., Serra, V., Calvo, M. T., Guzmán, M., Grueso, J., Aura, C. M., Pérez-García, J. M., Jessen, K., Liu, Y., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2750 · Cited by 158
MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients
Mattos‐Arruda, L. D., Bottai, G., Nuciforo, P. G., Tommaso, L. D., Giovannetti, E., Peg, V., Losurdo, A., Pérez-García, J. M., Masci, G., Corsi, F., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5495 · Cited by 156
PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer
Fujita, T., Doihara, H., Kawasaki, K., Takabatake, D., Takahashi, H., Washio, K., Tsukuda, K., Ogasawara, Y., & Shimizu, N. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6602926 · Cited by 156
Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition
Ortiz, M. A., Mikhailova, T., Li, X., Porter, B. A., Bah, A., & Kotula, L. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00750-x · Cited by 163
Current approaches and future directions in the treatment of HER2-positive breast cancer
Hurvitz, S. A., Hu, Y., O’Brien, N. A., & Finn, R. S. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.04.008 · Cited by 151
Molecular Mechanisms of ErbB2-Mediated Breast Cancer Chemoresistance
Tan, M., & Yu, D. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-74039-3_9 · Cited by 151
RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy
Fumagalli, D., Venet, D., Ignatiadis, M., Azim, H. A., Maetens, M., Rothé, F., Salgado, R., Bradbury, I., Pusztai, L., Harbeck, N., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.3824 · Cited by 151
ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer
Stern, D. F. (2008) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-008-9083-7 · Cited by 150
Inhibition of Activated Fibroblast Growth Factor Receptor 2 in Endometrial Cancer Cells Induces Cell Death Despite PTEN Abrogation
Byron, S. A., Gartside, M. G., Wellens, C. L., Mallon, M. A., Keenan, J. B., Powell, M. A., Goodfellow, P. J., & Pollock, P. M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0770 · Cited by 149
Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies
Colombo, M., Fiandra, L., Alessio, G., Mazzucchelli, S., Nebuloni, M., Palma, C. D., Kantner, K., Pelaz, B., Rotem, R., Corsi, F., et al. (2016) · Nature Communications · doi:10.1038/ncomms13818 · Cited by 149
Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy
Jain, S., Shah, A. N., Santa-Maria, C. A., Siziopikou, K. P., RADEMAKER, A. W., Helenowski, I., Cristofanilli, M., & Gradishar, W. J. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4792-0 · Cited by 151
Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases
Shah, N., Mohammad, A. S., Saralkar, P. A., Sprowls, S. A., Vickers, S. D., John, D. Q., Tallman, R. M., Lucke-Wold, B. P., Jarrell, K. L., Pinti, M. V., et al. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.021 · Cited by 149
Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer
Pályi‐Krekk, Z., Barok, M., Isola, J. J., Tammi, M., ̋si, J. S., & Nagy, P. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2007.08.018 · Cited by 149
Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins
Yoshimi, A., Goyama, S., Watanabe‐Okochi, N., Yoshiki, Y., Nannya, Y., Nitta, E., Arai, S., Sato, T., Shimabe, M., Nakagawa, M. M., et al. (2011) · Blood · doi:10.1182/blood-2009-12-261602 · Cited by 146
Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions
Liu, B., Fan, Z., Edgerton, S. M., Yang, X., Lind, S. E., & Thor, A. D. (2011) · Cell Cycle · doi:10.4161/cc.10.17.16359 · Cited by 120
PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib
Wang, L., Zhang, Q., Zhang, J., Sun, S., Guo, H., Jia, Z. Y., Wang, B., Shao, Z., Wang, Z., & Hu, X. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-248 · Cited by 149
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 151
Lapatinib Antitumor Activity Is Not Dependent upon Phosphatase and Tensin Homologue Deleted on Chromosome 10 in ErbB2-Overexpressing Breast Cancers
Xia, W., Husain, I., Liu, L.-H., Bacus, S. S., Saini, S., Spohn, J., Pry, K. J., Westlund, R. E., Stein, S. H., & Spector, N. L. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2101 · Cited by 147
IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells
Perks, C. M., Vernon, E. G., Rosendahl, A. H., Tonge, D. W., & Holly, J. M. P. (2007) · Oncogene · doi:10.1038/sj.onc.1210397 · Cited by 143
Strategies for Delaying or TreatingIn vivoAcquired Resistance to Trastuzumab in Human Breast Cancer Xenografts
du Manoir, J. M., Francia, G., Man, S., Mossoba, M. E., Medin, J. A., Viloria‐Petit, A., Hicklin, D. J., Emmenegger, U., & Kerbel, R. S. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1109 · Cited by 143
Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy
Amit, I., Wides, R., & Yarden, Y. (2007) · Molecular Systems Biology · doi:10.1038/msb4100195 · Cited by 147
The Changing Paradigm for the Treatment of HER2-Positive Breast Cancer
Patel, A., Unni, N. G., & Peng, Y. S. (2020) · Cancers · doi:10.3390/cancers12082081 · Cited by 147
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 146
Cross-Talk Between the ErbB/HER Family and the Type I Insulin-Like Growth Factor Receptor Signaling Pathway in Breast Cancer
Jin, Q., & Esteva, F. J. (2008) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-008-9107-3 · Cited by 143
Targeting PI3K Signaling in Combination Cancer Therapy
Tostivint, E. P., Thibault, B., & Guillermet‐Guibert, J. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.04.002 · Cited by 141
Intratumoral Delivery of IL-21 Overcomes Anti-Her2/Neu Resistance through Shifting Tumor-Associated Macrophages from M2 to M1 Phenotype
Xu, M. M., Liu, M., Du, X., Li, S., Li, H., Li, X., Li, Y., Wang, Y., Qin, Z., Fu, Y., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402603 · Cited by 146
Mechanisms of resistance to HER family targeting antibodies
Kruser, T. J., & Wheeler, D. L. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.01.009 · Cited by 142
Herceptin‐induced inhibition of ErbB2 signaling involves reduced phosphorylation of Akt but not endocytic down‐regulation of ErbB2
Longva, K. E., Pedersen, N. M., Haslekås, C., Stang, E., & Madshus, I. H. (2005) · International Journal of Cancer · doi:10.1002/ijc.21015 · Cited by 142
PI3K/Akt/mTOR inhibitors in breast cancer.
Lee, J. J. X., Loh, K. W.-J., & Yap, Y. S. (2015) · Europe PMC (PubMed Central) · doi:10.7497/j.issn.2095-3941.2015.0089 · Cited by 230
Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance
Saha, T., & Lukong, K. E. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.856974 · Cited by 148
Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation
Liang, K., Esteva, F. J., Albarracin, C., Stemke-Hale, K., Lu, Y., Bianchini, G., Yang, C.-Y., Li, Y., Li, X., Chen, C.-T., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.025 · Cited by 139
Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (Review)
Libra, M. (2011) · International Journal of Oncology · doi:10.3892/ijo.2011.1312 · Cited by 142
Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition
Rexer, B. N., Ham, A.-J. L., Rinehart, C., Hill, S., de Matos Granja-Ingram, N., González-Angulo, A. M., Mills, G. B., Dave, B., Chang, J. C., Liebler, D. C., et al. (2011) · Oncogene · doi:10.1038/onc.2011.130 · Cited by 139
The Evolving Landscape of HER2 Targeting in Breast Cancer
Moasser, M. M., & Krop, I. E. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.2286 · Cited by 135
Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer
Jérusalem, G., Fasolo, A., Dieras, V. C., Cardoso, F., Bergh, J. C. S., Vittori, L., Zhang, Y., Massacesi, C., Sahmoud, T., & Gianni, L. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-1260-x · Cited by 137
Deciphering the Role of PI3K/Akt/mTOR Pathway in Breast Cancer Biology and Pathogenesis
McAuliffe, P. F., Meric‐Bernstam, F., Mills, G. B., & Gonzalez-Angulo, A. M. (2010) · Clinical Breast Cancer · doi:10.3816/cbc.2010.s.013 · Cited by 136
PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab
Jensen, J. D., Knoop, A. S., Lænkholm, A., Grauslund, M., Jensen, M., Santoni‐Rugiu, E., Andersson, M., & Ewertz, M. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr546 · Cited by 135
Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence
Pandya, K., Meeke, K., Clementz, A. G., Rogowski, A., Roberts, J., Miele, L., Albain, K. S., & Osipo, C. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.321 · Cited by 135
Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment
Pasha, N., & Turner, N. C. (2021) · Nature Cancer · doi:10.1038/s43018-021-00229-1 · Cited by 135
EXEL-7647 Inhibits Mutant Forms of ErbB2 Associated with Lapatinib Resistance and Neoplastic Transformation
Trowe, T., Boukouvala, S., Calkins, K., Cutler, R. E., Fong, R., Funke, R. P., Gendreau, S. B., Kim, Y. D., Miller, N., Woolfrey, J. R., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4367 · Cited by 132
Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists
Yang, X. H., Flores, L. M., Li, Q., Zhou, P., Xu, F., Krop, I. E., & Hemler, M. E. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4032 · Cited by 134
Phase Ib Study of Buparlisib plus Trastuzumab in Patients with HER2-Positive Advanced or Metastatic Breast Cancer That Has Progressed on Trastuzumab-Based Therapy
Saura, C., Bendell, J. C., Jérusalem, G., Su, S., Ru, Q. C., Buck, S., Mills, D., Ruquet, S., Bosch, A., Urruticoechea, A., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1070 · Cited by 137
HER2-targeted therapy in breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors
Nielsen, D. L., Andersson, M., & Kamby, C. (2008) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2008.09.003 · Cited by 134
Multiplexed Cell Signaling Analysis of Human Breast Cancer Applications for Personalized Therapy
Wulfkuhle, J. D., Speer, R., Pierobon, M., Laird, J., Espina, V. A., Deng, J., Mammano, E., Yang, S. X., Swain, S. M., Nitti, D., et al. (2008) · Journal of Proteome Research · doi:10.1021/pr7008127 · Cited by 133
Epithelial–Mesenchymal Transition Programs and Cancer Stem Cell Phenotypes: Mediators of Breast Cancer Therapy Resistance
Gooding, A. J., & Schiemann, W. P. (2020) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-20-0067 · Cited by 141
Inhibition of Mammalian Target of Rapamycin Is Required for Optimal Antitumor Effect of HER2 Inhibitors against HER2-Overexpressing Cancer Cells
Miller, T. W., Forbes, J. T., Shah, C., Wyatt, S. K., Manning, H. C., Olivares, M. G., Sanchez, V. M., Dugger, T. C., Granja, N. D. M., Narasanna, A., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1665 · Cited by 130
Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy
Pham, P. V., Phan, N. L., Nhung, N. T., Truong, N. H., Duong, T. T., Le, D., Truong, K. D., & Phan, N. K. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-209 · Cited by 132
Trastuzumab, but Not Pertuzumab, Dysregulates HER2 Signaling to Mediate Inhibition of Autophagy and Increase in Reactive Oxygen Species Production in Human Cardiomyocytes
Mohan, N., Shen, Y., Endo, Y., ElZarrad, M. K., & Wu, W. J. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0741 · Cited by 137
Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance
Marina, M. E. (2014) · Frontiers in bioscience · doi:10.2741/4212 · Cited by 133
HER2-Positive Breast Cancer
Engel, R. H., & Kaklamani, V. (2007) · Drugs · doi:10.2165/00003495-200767090-00006 · Cited by 129
Targeting Akt in cancer therapy
LoPiccolo, J., Granville, C. A., Gills, J. J., & Dennis, P. A. (2007) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e3280cc2c6f · Cited by 129
Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors
Chakrabarty, A., Bhola, N. E., Sutton, C., Ghosh, R., Kuba, M. G., Dave, B., Chang, J. C., & Arteaga, C. L. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2440 · Cited by 130
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 135
Increased autophagy blocks HER2-mediated breast tumorigenesis
Vega-Rubín-de-Celis, S., Zou, Z., Fernández, Á. F., Ci, B., Kim, M., Xiao, G., Xie, Y., & Levine, B. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717800115 · Cited by 131
HER2 Phosphorylation Is Maintained by a PKB Negative Feedback Loop in Response to Anti-HER2 Herceptin in Breast Cancer
Gijsen, M., King, P., Perera, T., Parker, P. J., Harris, A. L., Larijani, B., & Kong, A. H. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000563 · Cited by 129
TGFα expression impairs Trastuzumab-induced HER2 downregulation
Valabrega, G., Montemurro, F., Sarotto, I., Petrelli, A., Rubini, P., Tacchetti, C., Aglietta, M., Comoglio, P. M., & Giordano, S. (2005) · Oncogene · doi:10.1038/sj.onc.1208478 · Cited by 129
Advances in Targeting Human Epidermal Growth Factor Receptor-2 Signaling for Cancer Therapy
Meric‐Bernstam, F., & Hung, M. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1732 · Cited by 129
Resistance and Overcoming Resistance in Breast Cancer
Luque-Bolivar, A., Pérez-Mora, E., Villegas, V. E., & Rondón‐Lagos, M. (2020) · Breast Cancer Targets and Therapy · doi:10.2147/bctt.s270799 · Cited by 139
The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies
Freudenberg, J. A., Wang, Q., Katsumata, M., Drebin, J. A., Nagatomo, I., & Greene, M. I. (2009) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2009.05.001 · Cited by 135
PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors
Mellinghoff, I. K., Cloughesy, T. F., & Mischel, P. S. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1992 · Cited by 130
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
Outcome of Patients with HER2-Positive Advanced Breast Cancer Progressing During Trastuzumab-Based Therapy
Montemurro, F., Donadio, M., Clavarezza, M., Redana, S., Jacomuzzi, M. E., Valabrega, G., Danese, S., Vietti-Ramus, G., Durando, A., Venturini, M., et al. (2006) · The Oncologist · doi:10.1634/theoncologist.11-4-318 · Cited by 123
Suppression of HER2/HER3-Mediated Growth of Breast Cancer Cells with Combinations of GDC-0941 PI3K Inhibitor, Trastuzumab, and Pertuzumab
Yao, E. S., Zhou, W., Lee-Hoeflich, S. T., Truong, T., Haverty, P. M., Eastham‐Anderson, J., Lewin‐Koh, N., Gunter, B., Belvin, M. P., Murray, L. J., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2814 · Cited by 125
Src Family Kinases as Novel Therapeutic Targets to Treat Breast Cancer Brain Metastases
Zhang, S., Huang, W.-C., Zhang, L., Zhang, C., Lowery, F. J., Ding, Z., Guo, H., Wang, H., Huang, S., Şahin, A. A., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-1803 · Cited by 125
P2X7 Integrates PI3K/AKT and AMPK-PRAS40-mTOR Signaling Pathways to Mediate Tumor Cell Death
Shu, B., Sun, X., Bai, A., Zhang, C., Li, L., Enjyoji, K., JUNGER, W. G., Robson, S. C., & Wu, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060184 · Cited by 132
The therapeutic potential of mTOR inhibitors in breast cancer
Steelman, L. S., Martelli, A. M., Cocco, L., Libra, M., Nicoletti, F., Abrams, S. L., & McCubrey, J. A. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12958 · Cited by 124
Functional miRNAs in breast cancer drug resistance
Hu, W., Tan, C., He, Y., Zhang, G., Xu, Y., & Tang, J. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s152462 · Cited by 126
The Breast Cancer Stem Cells Traits and Drug Resistance
Zheng, Q., Zhang, M., Zhou, F., Zhang, L., & Meng, X. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.599965 · Cited by 133
Selective Targeting of Cancer Stem Cells
Körkaya, H., & Wicha, M. S. (2007) · BioDrugs · doi:10.2165/00063030-200721050-00002 · Cited by 126
Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R
Ye, X., Zhu, H., Bai, W., Wang, T., Wang, L., Chen, Y., Yang, A., & Jia, L. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-134 · Cited by 124
An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin
Garner, A. P., Bialucha, C. U., Sprague, E. R., Garrett, J. T., Sheng, Q., Li, S., Sineshchekova, O., Saxena, P., Sutton, C. R., Chen, D., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1198 · Cited by 125
Inhibitors of HSP90 block p95-HER2 signaling in Trastuzumab-resistant tumors and suppress their growth
Chandarlapaty, S., Scaltriti, M., Angelini, P. D., Ye, Q., Guzmán, M., Hudis, C. A., Norton, L., Solit, D. B., Arribas, J., Baselga, J. M., et al. (2009) · Oncogene · doi:10.1038/onc.2009.337 · Cited by 125
A new mechanism of trastuzumab resistance in gastric cancer: MACC1 promotes the Warburg effect via activation of the PI3K/AKT signaling pathway
Liu, J., Pan, C., Guo, L., Wu, M., Guo, J., Peng, S., Wu, Q., & Zuo, Q. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0302-1 · Cited by 129
Selective Inhibition of ErbB2-Overexpressing Breast Cancer In vivo by a Novel TAT-Based ErbB2-Targeting Signal Transducers and Activators of Transcription 3–Blocking Peptide
Tan, M., Lan, K., Yao, J., Lu, C., Sun, M., Neal, C. L., Lü, J., & Yu, D. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2747 · Cited by 123

Authors: Nagata, Y., Lan, K.-H., Zhou, X., Tan, M., Esteva, F. J., Sahin, A. A., Klos, K. S., Li, P., Monia, B. P., Nguyen, N. T., Hortobagyi, G. N., Hung, M.-C., & Yu, D.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Ionis Pharmaceuticals (United States) (US)
Corresponding author: Yu, Dihua
ORCID: Lan, Keng-Hsueh
Zhou, Xiaoyan
Tan, Ming
Esteva, Francisco J.
Li, Ping
Monia, Brett P.
Hung, Mien-Chie
Yu, Dihua
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2004-08
Volume: 6
Issue: 2
Pages: 117-127
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2004.06.022
OpenAlex: W2059411043
Cited by: 1,858
References: 70
Citations by year: 2026: 19 · 2025: 29 · 2024: 35 · 2023: 82 · 2022: 52 · 2021: 50 · 2020: 60 · 2019: 56 · 2018: 66 · 2017: 68 · 2016: 88 · 2015: 109 · 2014: 119 · 2013: 125 · 2012: 123
FWCI: 43.34
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3272 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ca060488-09)
National Cancer Institute (P01CA099031, 2R01-CA60488, P30CA016672)
Topics: Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: PTEN, trastuzumab, trastuzumab resistance, ERBB2, HER2-positive breast cancer, Src kinase inhibition, PI3K inhibitors, predictive biomarkers, antisense oligonucleotides
MeSH terms: Trastuzumab, Phosphoinositide-3 Kinase Inhibitors, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Enzyme Activation, Enzyme Inhibitors, Female, Humans, Mice, Nude, Neoplasm Transplantation, Phosphoric Monoester Hydrolases, Proto-Oncogene Proteins, Genes, Tumor Suppressor, Oligonucleotides, Antisense, Protein Serine-Threonine Kinases, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, src-Family Kinases, Phosphatidylinositol 3-Kinases, Tumor Suppressor Proteins, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, Antibodies, Monoclonal, Humanized

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 activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks