The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Activity of the Dual Kinase Inhibitor Lapatinib (GW572016) against HER-2-Overexpressing and Trastuzumab-Treated Breast Cancer Cells
Abstract
Lapatinib (GW572016) is a selective inhibitor of both epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases. Here, we explore the therapeutic potential of lapatinib by testing its effect on tumor cell growth in a panel of 31 characterized human breast cancer cell lines, including trastuzumab-conditioned HER-2-positive cell lines. We further characterize its activity in combination with trastuzumab and analyze whether EGFR and HER-2 expression or changes induced in the activation of EGFR, HER-2, Raf, AKT, or extracellular signal-regulated kinase (ERK) are markers of drug activity. We report that concentration-dependent antiproliferative effects of lapatinib were seen in all breast cancer cell lines tested but varied significantly between individual cell lines with up to 1,000-fold difference in the IC50s (range, 0.010-18.6 μmol/L). Response to lapatinib was significantly correlated with HER-2 expression and its ability to inhibit HER-2, Raf, AKT, and ERK phosphorylation. Long-term in vivo lapatinib studies were conducted with human breast cancer xenografts in athymic mice. Treatment over 77 days resulted in a sustained and significant reduction in xenograft volume compared with untreated controls. For the combination of lapatinib plus trastuzumab, synergistic drug interactions were observed in four different HER-2-overexpressing cell lines. Moreover, lapatinib retained significant in vitro activity against cell lines selected for long-term outgrowth (>9 months) in trastuzumab-containing (100 μg/mL) culture medium. These observations provide a clear biological rationale to test lapatinib as a single agent or in combination with trastuzumab in HER-2-overexpressing breast cancer and in patients with clinical resistance to trastuzumab. (Cancer Res 2006; 66(3): 1630-9)
Overview
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
Cites
Statistics
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Self-citationSlamon, 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
Self-citationUntangling the ErbB signalling network
Yarden, Y., & Sliwkowski, M. X. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052073 · Cited by 6,974
Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian Cancer
Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J. A., Wong, S. G., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, J., Ullrich, A., et al. (1989) · Science · doi:10.1126/science.2470152 · Cited by 6,816
Self-citationInhibitory 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 · cited 1×
“Such strategies in the clinical setting could add more effective inhibition of the receptor tyrosine kinase to an additional important mechanism of action of trastuzumab thought to occur through immune effector cells (48).”
BackgroundOlayioye, M. A. (2000) · The EMBO Journal · doi:10.1093/emboj/19.13.3159 · Cited by 2,434
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
Self-citationNagata, 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 · cited 1×
“A detailed analysis of HER-2 receptor phosphorylation following short treatment of SK-BR-3 and BT474 cells with trastuzumab, however, reveals a moderate increase of HER-2 tyrosine phosphorylation by trastuzumab treatment (45).”
Graus-Porta, D. (1997) · The EMBO Journal · doi:10.1093/emboj/16.7.1647 · Cited by 1,590
A Unique Structure for Epidermal Growth Factor Receptor Bound to GW572016 (Lapatinib)
Wood, E. R., Truesdale, A. T., McDonald, O. B., Yuan, D., Hassell, A., Dickerson, S. H., Ellis, B., Pennisi, C., Horne, E., Lackey, K., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1168 · Cited by 1,122
Self-citation
Cited by
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950
Self-citationLapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Geyer, C. E., Forster, J., Lindquist, D., Chan, S., Romieu, C. G., Pienkowski, T., Jagiello-Gruszfeld, A., Crown, J., Chan, A., Kaufman, B., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa064320 · Cited by 3,425
Self-citationSystematic identification of genomic markers of drug sensitivity in cancer cells
Garnett, M. J., Edelman, E. J., Heidorn, S. J., Greenman, C. D., Dastur, A., Lau, K. W., Greninger, P., Thompson, I. R., Luo, X., Soares, J., et al. (2012) · Nature · doi:10.1038/nature11005 · Cited by 2,456
Baselga, J., Bradbury, I., Eidtmann, H., Di Cosimo, S., de Azambuja, E., Aura, C., Gómez, H., Dinh, P., Fauria, K., Van Dooren, V., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(11)61847-3 · Cited by 1,317
Self-citationTargeting HER2-positive breast cancer: advances and future directions
Swain, S. M., Shastry, M., & Hamilton, E. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00579-0 · Cited by 1,160
Metadata
- Authors
- Konecny, G. E., Pegram, M. D., Venkatesan, N., Finn, R., Yang, G., Rahmeh, M., Untch, M., Rusnak, D. W., Spehar, G., Mullin, R. J., Keith, B. R., Gilmer, T. M., Berger, M., Podratz, K. C., & Slamon, D. J.
- Venue
- Cancer Research
- Published
- 2006-02-01
- Volume
- 66
- Issue
- 3
- Pages
- 1630-1639
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2145477245
- Cited by
- 914
- References
- 47
- FWCI
- 33.02
- Type
- journal article
- Language
- en
- Open access
- closed
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Activity of the Dual Kinase Inhibitor Lapatinib (GW572016) against HER-2-Overexpressing and Trastuzumab-Treated Breast Cancer Cells. https://app.cochat.ai/papers/10.1158/0008-5472.can-05-1182
- The paper
- Konecny, G. E., Pegram, M. D., Venkatesan, N., Finn, R., Yang, G., Rahmeh, M., Untch, M., Rusnak, D. W., Spehar, G., Mullin, R. J., Keith, B. R., Gilmer, T. M., Berger, M., Podratz, K. C., & Slamon, D. J. (2006). Activity of the Dual Kinase Inhibitor Lapatinib (GW572016) against HER-2-Overexpressing and Trastuzumab-Treated Breast Cancer Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-05-1182
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
