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Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941

, : Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15(5): 429-440

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.


PMID: 19411071

DOI: 10.1016/j.ccr.2009.03.020

Other references

Ross, D.J., 1981: Invertase, amylase, and respiratory activities of a soil profile under a kauri tree in North Aukland, New Zealand: a note. Enzyme activities under Agathis australis were similar to those in another soil under Nothofagus truncata [see FA 35, 1218], and suggested that A. australis contributed directly to invertase but not to amylase activity. On an organic C basis, enzy...

Bjornn T.C., 1977: Wild fish production and management. Schwiebert, Ernest (Ed ) American Fisheries Society Special Publication, No 10 Columbia River Salmon And Steelhead Proceedings Of A Symposium Vancouver, Wash , Usa, March 5-6, 1976 Viii+214p Illus Maps American Fisheries Society: Washington, D C , Usa 65-71

Poulson T.L.; Platt W.J., 1989: Gap light regimes influence canopy tree diversity. Ecology (Washington D C) 70(3): 533-555, 569-576

Claude, H.; Baruk, H.; Olivier, H R., 1932: Polypeptidorachie et insuffisance hepatique dans le som-meil cataleptique et dans la stupeur catatonique. In 7 of 9 cases of cataleptic sleep and catatonic coma there was marked increase in the cleavage index of cerebrospinal fluid, which was frequently associated with hepatic insufficiency.

Nabelek, A.K.; Tampas, J.W.; Burchfield, S.B., 2004: Comparison of speech perception in background noise with acceptance of background noise in aided and unaided conditions. Background noise is a significant factor influencing hearing-aid satisfaction and is a major reason for rejections of hearing aids. Attempts have been made by previous researchers to relate the use of hearing aids to speech perception in noise (SP...

Frederick, W.R.; Delapenha, R.; Gray, G.; Greaves, W.L.; Saxinger, C., 1987: HIV testing of surrogate mothers. New England Journal of Medicine 317(21): 1351-1352

Calder, R.S.D.; Schartup, A.T.; Li, M.; Valberg, A.P.; Balcom, P.H.; Sunderland, E.M., 2016: Future Impacts of Hydroelectric Power Development on Methylmercury Exposures of Canadian Indigenous Communities. NlmCategory="UNASSIGNED">Developing Canadian hydroelectric resources is a key component of North American plans for meeting future energy demands. Microbial production of the bioaccumulative neurotoxin methylmercury (MeHg) is stimulat...

Fike, J.R.; Mizumatsu, S.; Morhardt, D.; Rola, R.; Raber, J., 2003: Ionizing radiation causes long-term inhibition of neurogenesis in the dentate gyrus. Journal of Neurochemistry 85(Supplement 1): 3, May

Warner, M.D.; Azmi, I.F.; Zhao, Y.; Kang, S.; Bell, S.P., 2017: Replication origin flanking roadblocks reveal origin-licensing dynamics and altered sequence dependence. In eukaryotes, DNA replication initiates from multiple origins of replication for timely genome duplication. These sites are selected by origin licensing, during which the core enzyme of the eukaryotic DNA replicative helicase, the Mcm2-7 (minichr...

Olivares, O.; Campos, R., 1966: Bronchopulmonary pseudotumor caused by a bronchial foreign body. Revista Medica de Chile 94(4): 242-244