| Literature DB >> 19411071 |
Teemu T Junttila1, Robert W Akita, Kathryn Parsons, Carter Fields, Gail D Lewis Phillips, Lori S Friedman, Deepak Sampath, Mark X Sliwkowski.
Abstract
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.Entities:
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Year: 2009 PMID： 19411071 DOI： 10.1016/j.ccr.2009.03.020
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743