Direct visualization of heterogeneous extravascular distribution of trastuzumab in human epidermal growth factor receptor type 2 overexpressing xenografts.

Treatment of HER-2/neu overexpressing breast cancer xenograft models with trastuzumab (Herceptin) and gefitinib (ZD1839): drug combination effects on tumor growth, HER-2/neu and epidermal growth factor receptor expression, and viable hypoxic cell fraction.

PURPOSE The purpose of this research was to assess the effects of single agent and combination treatment with trastuzumab and gefitinib on tumor growth and tumor microenvironment in two HER-2/neu overexpressing breast xenograft models, MDA-MB-435/LCC6(HER-2) (LCC6(HER-2); estrogen receptor negative) and MCF-7(HER-2) (estrogen receptor positive). EXPERIMENTAL DESIGN LCC6(HER-2) and MCF-7(HER-2...

Superior antitumor activity of a novel bispecific antibody cotargeting human epidermal growth factor receptor 2 and type I insulin-like growth factor receptor.

The humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin; Genentech) effectively inhibits human epidermal growth factor receptor 2 (HER2)-positive breast tumors. However, many patients responding to treatment often develop resistance. Cross-talk between type I insulin-like growth factor receptor (IGF-IR) and HER2 and elevated IGF-IR signaling have been implicated in tumor cell r...

Bone morphogenic protein receptor type 1a (BMPR1A) and Caveolin-1 associated with trastuzumab resistance of breast cancer cells

Trastuzumab is a specific monoclonal antibody used for therapeutic of the human epidermal growth factor receptor 2 (HER-2) -positive metastatic breast cancer. But, resistance to trastuzumab is a major obstacle in clinical efficiency.  During the past years, several studies have been done to find the mechanisms contributing to trastuzumab resistance. Previous studies have highlighted that bone m...

A specific vascular endothelial growth factor receptor tyrosine kinase inhibitor enhances the antiproliferative effect of trastuzumab in human epidermal growth factor receptor 2 overexpressing breast cancer cell lines

Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2-overexpressing tumor cells.

The monoclonal antibody trastuzumab (Herceptin) directed against the human epidermal growth factor receptor 2 (HER2) results in tumor regressions when administered to patients with HER2-overexpressing breast cancer. One of the underlying mechanisms of this antibody-induced tumor regression is based on the internalization and degradation of HER2 by tumor cells on interaction with trastuzumab, su...