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The anti-HER3 antibody in combination with trastuzumab exerts synergistic antitumor activity in HER2-positive gastric cancer.
- Source :
-
Cancer Letters . Sep2016, Vol. 380 Issue 1, p20-30. 11p. - Publication Year :
- 2016
-
Abstract
- The anti-HER2 monoclonal antibody trastuzumab is central to the treatment of HER2-positive gastric cancer (GC); however, its responses are limited. HER3 seems to be the preferred dimerization partner with HER2 and is emerging as a key target for complete blockade of downstream pathways and better clinical response. In this study, we report that novel anti-HER3 antibodies (1A5-3D4) that can neutralize multiple modes of HER3 activation, combined with trastuzumab, exhibited synergistic inhibitory effect on the cell proliferation in HER2-positive GC cell lines. Follow-up studies revealed that the combination treatment significantly inhibited phosphorylation of HER3 as well as AKT and ERK signals. In vivo experiments further showed that the anti-tumor effect of trastuzumab was enhanced by its combination with 1A5-3D4 in NCI-N87 xenograft and patient derived xenografts (PDX). Particularly in an HER2-negative whereas neuregulin1 (a ligand of HER3) positive PDX, the combination was also superior to monotherapy. 1A5-3D4 in combination with trastuzumab exhibits a synergistic inhibitory effect on tumor activity, suggesting that targeting both HER2 and HER3 resulted in an improved treatment effects on HER2-positive GC. [ABSTRACT FROM AUTHOR]
- Subjects :
- *STOMACH cancer treatment
*TRASTUZUMAB
*ANTINEOPLASTIC agents
*COMBINATION drug therapy
*CANCER cell proliferation
*THERAPEUTICS
*ANIMAL experimentation
*CELL lines
*CELL physiology
*CELL receptors
*CELLULAR signal transduction
*DRUG therapy
*DRUG synergism
*DOSE-effect relationship in pharmacology
*GROWTH factors
*MICE
*PHOSPHORYLATION
*PHOSPHOTRANSFERASES
*STOMACH tumors
*TRANSFERASES
*TUMORS
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 380
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 117038273
- Full Text :
- https://doi.org/10.1016/j.canlet.2016.06.005