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A Functional Genetic Approach Identifies the PI3K Pathway as a Major Determinant of Trastuzumab Resistance in Breast Cancer
Open accessAbstract
A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA (activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy.
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“Patients with ‘hot spot’ PIK3CA mutations and undetectable or low PTEN measured by IHC, exhibited a poorer outcome after treatment with chemotherapy and trastuzumab compared to patients without those alterations (Berns et al., 2007; Dave et al., 2011; Esteva et al., 2010).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Berns et al., 2007
In the citing paper
“Using a large-scale siRNA genetic screen, they identified PTEN as the only gene whose knockdown conferred trastuzumab resistance (Berns et al., 2007).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Berns et al., 2007
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Cites
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
Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets
Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000) · Nature Medicine · doi:10.1038/74704 · Cited by 2,768
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
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
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., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.022 · Cited by 1,858
A transforming mutation in the pleckstrin homology domain of AKT1 in cancer
Carpten, J. D., Faber, A. L., Horn, C. L., Donoho, G. P., Briggs, S., Robbins, C. M., Hostetter, G. H., Boguslawski, S. J., Moses, T. Y., Savage, S., et al. (2007) · Nature · doi:10.1038/nature05933 · Cited by 1,322
A large-scale RNAi screen in human cells identifies new components of the p53 pathway
Berns, K., Hijmans, E. M., Mullenders, J., Brummelkamp, T. R., Velds, A., Heimerikx, M., Kerkhoven, R. M., Madiredjo, M., Nijkamp, W., Weigelt, B., et al. (2004) · Nature Cell Biology · doi:10.1038/nature02371 · Cited by 1,080
Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3
Sergina, N. V., Rausch, M., Wang, D., Blair, J. A., Hann, B. C., Shokat, K. M., & Moasser, M. M. (2007) · Nature · doi:10.1038/nature05474 · Cited by 993
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
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
Neu-Protein Overexpression in Breast Cancer
van de Vijver, M. J., Peterse, J. L., Mooi, W. J., Wisman, P., Lomans, J., Dalesio, O., & Nusse, R. (1988) · New England Journal of Medicine · doi:10.1056/nejm198811103191902 · Cited by 860
Molina, M. A., Codony‐Servat, J., Albanell, J., Rojo, F., Arribas, J., & Baselga, J. M. (2001) · PubMed · Cited by 766
Kortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · cited 1×
“Importantly, a second, independent shRNA knocking down PTEN expression (Kortlever et al., 2006) also conferred resistance to trastuzumab, effectively ruling out the possibility that ‘‘off target’’ effects of the shRNA vectors caused the resistance phenotype (Figure 2A).”
BackgroundYakes, F. M., Chinratanalab, W., Ritter, C. A., King, W., SEELIG, S. A., & Arteaga, C. L. (2002) · PubMed · Cited by 608
Breast Cancer–Associated PIK3CA Mutations Are Oncogenic in Mammary Epithelial Cells
Isakoff, S. J., Engelman, J. A., Irie, H. Y., Luo, J., Brachmann, S. M., Pearline, R. V., Cantley, L. C., & Brugge, J. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2612 · Cited by 505
Overexpression of p53 and prognosis in breast cancer
Friedrichs, K., Gluba, S., Eidtmann, H., & Jonat, W. (1993) · Cancer · doi:10.1002/1097-0142(19931215)72:12 · Cited by 210
An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors
Brummelkamp, T. R., Fabius, A. W. M., Mullenders, J., Madiredjo, M., Velds, A., Kerkhoven, R. M., Bernards, R., & Beijersbergen, R. L. (2006) · Nature Chemical Biology · doi:10.1038/nchembio774 · Cited by 190
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
Chui, X., Egami, H., Yamashita, J., Kurizaki, T., Ohmachi, H., Yamamoto, S., & Ogawa, M. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.236 · Cited by 117
Hannemann, J., Kristel, P., van Tinteren, H., Bontenbal, M., van Hoesel, Q. G. C. M., Smit, W. M., Nooij, M. A., Voest, E. E., van der Wall, E., Hupperets, P. S. G. J., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603449 · Cited by 62
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Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,785
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Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S. (2014) · Cancers · doi:10.3390/cancers6031769 · Cited by 2,463
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He, Y., Sun, M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00828-5 · Cited by 2,045
Metadata
- Authors
- Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., Beijersbergen, R. L., Mills, G. B., van de Vijver, M. J., & Bernards, R.
- Affiliations
- The Netherlands Cancer Institute (NL)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Bernards, René
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 12
- Issue
- 4
- Pages
- 395-402
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2020372547
- Cited by
- 1,627
- References
- 22
- Citations by year
- 2026: 26 · 2025: 44 · 2024: 33 · 2023: 81 · 2022: 69 · 2021: 54 · 2020: 63 · 2019: 70 · 2018: 88 · 2017: 74 · 2016: 102 · 2015: 116 · 2014: 118 · 2013: 144 · 2012: 123
- FWCI
- 37.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- trastuzumab resistance, breast cancer, PI3K signaling, PTEN, PIK3CA mutation, RNAi screen, drug sensitivity, prognostic factors, HER2-positive breast cancer, treatment response prediction
- MeSH terms
- Trastuzumab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Middle Aged, Mutation, Transduction, Genetic, Biomarkers, Tumor, Cohort Studies, Signal Transduction, Gene Expression Regulation, Neoplastic, Treatment Outcome, Disease Progression, Patient Selection, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, PTEN Phosphohydrolase, Kaplan-Meier Estimate, Class I Phosphatidylinositol 3-Kinases, Antibodies, Monoclonal, Humanized
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