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 accessAbstract
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.
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“In one early study in patients with metastatic breast cancer, loss or low levels of PTEN correlated with a lower response to trastuzumab (Nagata et al., 2004).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Nagata et al., 2004
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Cites
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
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
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
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
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
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
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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
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Facts and controversies in the use of trastuzumab in the adjuvant setting
Dinh, P., de Azambuja, E., Cardoso, F., & Piccart-Gebhart, M. J. (2008) · Nature Clinical Practice Oncology · doi:10.1038/ncponc1219 · Cited by 19
Metadata
- 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
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 6
- Issue
- 2
- Pages
- 117-127
- ISSN
- 1535-6108 (ISSN-L)
- 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
- 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
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