The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941
Open accessAbstract
Herceptin (trastuzumab) is the backbone of HER2-directed breast cancer therapy and benefits patients in both the adjuvant and metastatic settings. Here, we describe a mechanism of action for trastuzumab whereby antibody treatment disrupts ligand-independent HER2/HER3 interactions in HER2-amplified cells. The kinetics of dissociation parallels HER3 dephosphorylation and uncoupling from PI3K activity, leading to downregulation of proximal and distal AKT signaling, and correlates with the antiproliferative effects of trastuzumab. A selective and potent PI3K inhibitor, GDC-0941, is highly efficacious both in combination with trastuzumab and in the treatment of trastuzumab-resistant cells and tumors.
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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
Chou, T.-C., & Talalay, P. (1984) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(84)90007-4 · Cited by 7,178
ERBB receptors and cancer: the complexity of targeted inhibitors
Hynes, N. E., & Lane, H. A. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1609 · Cited by 3,313
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 · cited 2×
“Evidence for the importance of Fc-FcgRIII involvement in the mechanism of action of trastuzumab is provided by Clynes et al. (2000), who assessed trastuzumab response in tumor models deficient in FcgRIII function.”
BackgroundCobleigh, M. A., Vogel, C. L., Tripathy, D., Robert, N. J., Scholl, S., Fehrenbacher, L., Wolter, J. M., Paton, V., Shak, S., Lieberman, G., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.9.2639 · Cited by 2,765
The selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., Mclauchlan, H., Klevernic, I., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,520
Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery
Hennessy, B. T., Smith, D. L., Ram, P. T., Lu, Y., & Mills, G. B. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1902 · Cited by 2,185
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 · cited 6×
“Furthermore, trastuzumab is reported to have either no effect on HER2 activation status or to cause a rapid increase or decrease of HER2 phosphorylation (Lane et al., 2000; Nagata et al., 2004; Sarup et al., 1991).”
BackgroundResultInfluentialTargeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate
Lewis Phillips, G. D., Li, G., Dugger, D. L., Crocker, L. M., Parsons, K. L., Mai, E., Blättler, W. A., Lambert, J. M., Chari, R. V. J., Lutz, R. J., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1776 · Cited by 1,676
Self-citation
Cited by
Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer
Baselga, J., Cortés, J., Kim, S.-B., Im, S.-A., Hegg, R., Im, Y.-H., Roman, L., Pedrini, J. L., Pienkowski, T., Knott, A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113216 · Cited by 2,532
Gianni, L., Pienkowski, T., Im, Y.-H., Roman, L., Tseng, L.-M., Liu, M.-C., Lluch, A., Staroslawska, E., de la Haba-Rodriguez, J., Im, S.-A., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70336-9 · Cited by 2,374
Targeting PI3K/Akt signal transduction for cancer therapy
He, Y., Sun, M. 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 1,892
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
The PI3K Pathway As Drug Target in Human Cancer
Courtney, K. D., Corcoran, R. B., & Engelman, J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.3641 · Cited by 1,237
Metadata
- Authors
- Junttila, T. T., Akita, R. W., Parsons, K., Fields, C., Lewis Phillips, G. D., Friedman, L. S., Sampath, D., & Sliwkowski, M. X.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 15
- Issue
- 5
- Pages
- 429-440
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1971267920
- Cited by
- 829
- References
- 36
- FWCI
- 30.58
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Junttila, T. T., Akita, R. W., Parsons, K., Fields, C., Lewis Phillips, G. D., Friedman, L. S., Sampath, D., & Sliwkowski, M. X. (2009). Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941. Cancer Cell. https://doi.org/10.1016/j.ccr.2009.03.020
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