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Tumor region-specific microarray analysis according to trastuzumab distribution in breast cancer patient derived xenograft

ABSTRACT: Our novel drug imaging technique revealed that trastuzumab, which is representative antibody drug for breast and gastric cancer in clinical, distributed heterogeneously inside tumor even though its target receptor, HER2 (Human epidermal growth factor receptor 2) expressed homogeneously. For identifying a predominant regulator of trastuzumab tumor delivery in the tumor site, we tried tumor region-specific microarray analysis according to trastuzumab distribution in patient derived xenograft model.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121787 | GEO | 2019/11/01

REPOSITORIES: GEO

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RNA sequencing of BT474 cells treated with trastuzumab or trastuzumab + pertuzumab and BT474-derived cells resistant to trastuzumab or trastuzumab + pertuzumab

Project description:We sequenced untreated BT474 cells, BT474 cells treated for three days with trastuzumab or trastuzumab + pertuzumab, as well as two BT474-derived trastuzumab-resistant pools and two BT474-derived trastuzumab + pertuzumab resistant pools. Resistant pools were generated by culturing BT474 cells in gradually increasing doses of trastuzumab and trastuzumab + pertuzumab over the course of several months and continually maintained in drug.

2020-01-26 | GSE121105 | GEO

Treatment effects of trastuzumab and TDM-1 in a murine model of breast cancer brain metastasis

Project description:Background: Central nervous system (CNS) metastases represent a major problem in the treatment of HER2-positive breast cancer due to the disappointing efficacy of HER2-targeted therapies in the brain microenvironment. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in preclinical models of brain metastases. Methods: We treated mice bearing BT474 or MDA-MB-361 tumors in the CNS (N=9-11 per group), or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histological analysis we determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling. All statistical tests were two-sided. Results: T-DM1 significantly delayed the growth of HER2-positive breast cancer brain metastases compared to trastuzumab. These findings were consistent between HER2-driven and PI3K-driven tumors. The activity of T-DM1 resulted in a striking survival benefit (median survival for BT474 tumors: 28d for trastuzumab vs 112d for T-DM1, HR=6.2, 95% CI=6.1 to 85.84; P<.001). No difference in drug distribution and HER2-signaling was revealed between the two groups. However, T-DM1 led to a significant increase in tumor cell apoptosis (One-way ANOVA for ApopTag, p<.001), which was associated with mitotic catastrophe. Conclusions: T-DM1 can overcome resistance to trastuzumab therapy in HER2-driven and PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component. Clinical investigation of T-DM1 for patients with CNS metastases from HER2-positive breast cancer is warranted. Comparison of trastuzumab (n=4) and TDM-1 (n=4) treated BT-474 human breast carcinoma cells growing in murine brain

2015-11-09 | E-GEOD-69042 | biostudies-arrayexpress

mRNA profiling reveals determinants of trastuzumab efficiency in HER2-positive breast cancer

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2015-04-21 | E-GEOD-55005 | biostudies-arrayexpress

Treatment effects of trastuzumab and TDM-1 in a murine model of breast cancer brain metastasis

2015-11-09 | GSE69042 | GEO

Tumor region-specific microarray analysis according to trastuzumab distribution in breast cancer patient derived xenograft

Project description:Tumor region-specific microarray analysis according to trastuzumab distribution in breast cancer patient derived xenograft

| PRJNA498427 | ENA

mRNA profiling reveals determinants of trastuzumab efficiency in HER2-positive breast cancer

2015-04-21 | GSE55005 | GEO

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HDAC inhibitor panobinostat engages host immune defenses to promote the tumoricidal effects of trastuzumab in HER2+ tumors

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2017-02-10 | GSE81380 | GEO

Gene expression profiling of primary HER2-positive breast cancers before and after brief exposure to single agent neoadjuvant trastuzumab

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2019-05-21 | GSE114082 | GEO

Gene expression profiling of primary HER2-positive breast cancers treated with adjuvant trastuzumab

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2015-10-19 | E-GEOD-55348 | biostudies-arrayexpress

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