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Herceptin (Trastuzumab) Research

13:04 EDT 18th October 2018 | BioPortfolio

Stimulation of natural killer cells with rhCD137 ligand enhances tumor-targeting antibody efficacy in gastric cancer.

Although many anticancer agents for gastric cancer have been developed, the prognosis for many patients remains poor. Recently, costimulatory immune molecules that reactivate antitumor immune responses by utilizing the host immune system have attracted attention as new therapeutic strategies. CD137 is a costimulatory molecule that reportedly potentiates the antitumor activity of tumor-targeting mo...

One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis.

One year is the standard duration of adjuvant trastuzumab for human epidermal receptor-2 (HER2) positive (HER2+) breast cancer (BC). Indeed, a shorter duration of trastuzumab can reduce cardiotoxicity and the costs involved and could provide the same benefit as a one-year treatment. We evaluated the available evidence from randomised controlled trials (RCTs) by comparing 1 year versus a shorter d...

Phosphorylated HER3 and FITC-labeled trastuzumab immunohistochemistry in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.

The development of trastuzumab has significantly improved the prognosis of HER2-positive breast cancer. However, disease recurs in some patients with HER2-positive breast cancer. A new strategy for treating HER2-positive breast cancer is necessary. Although several studies have reported that HER3 is a prognostic factor for HER2-positive breast cancers, phosphorylated HER3 (pHER3) has not been well...

Trastuzumab decorated TPGS-g-chitosan nanoparticles for targeted breast cancer therapy.

Breast cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) has led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, n...

Validation of CPS+EG, Neo-Bioscore, and modified Neo-Bioscore staging systems after preoperative systemic therapy of breast cancer: Protocol of a retrospective multicenter cohort study in China.

Prognostic assessment after preoperative systemic therapy (PST) is critical to develop a therapeutic strategy for breast cancer management. Currently, a clinical-pathologic staging system that incorporates ER status and nuclear grading (CPS + EG), and the Neo-Bioscore system that includes HER2 status into CPS + EG, are used to predict outcomes in patients with breast cancer after PST. Whil...

Assessment of the higher order structure of Humira®, Remicade®, Avastin®, Rituxan®, Herceptin®, and Enbrel® by 2D-NMR fingerprinting.

The advent of monoclonal antibody biosimilar products has stimulated the development of analytical methods that can better characterize an important quality attribute, namely the higher order structure (HOS). Here, we propose a simple approach based on heteronuclear 2D NMR techniques at natural abundance for generating spectral fingerprints of the HOS at high resolution. We show that the proposed ...

Optimal treatment of early stage HER2-positive breast cancer.

Significant advances have occurred in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer that have changed its natural history. The addition of trastuzumab to standard therapy has dramatically improved the prognosis for patients with early stage, HER2-positive breast cancer to unprecedented survival outcomes. Yet, long-term follow-up data from adjuvant pivotal ...

Immune Checkpoint Inhibition Overcomes ADCP-Induced Immunosuppression by Macrophages.

Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) critically contribute to the efficacy of anti-tumor therapeutic antibodies. We report here an unexpected finding that macrophages after ADCP inhibit NK cell-mediated ADCC and T cell-mediated cytotoxicity in breast cancers and lymphomas. Mechanistically, AIM2 is recruited to the phagosomes by FcγR ...

Patient-derived organoids: New co-clinical model to predict treatment response in cancer?

One of the most relevant problems in clinical oncology is to know the response of each patient to the different treatments available, to be able to choose the best therapy, or combination of them, at the opportune moment once the cancer is diagnosed. Twenty years ago, trastuzumab was approved as therapy for breast cancer, an antibody directed specifically against the Her2 receptor that only a grou...

Use of data-mining to support real-world cost analyses: An example using HER2-positive breast cancer in Iran.

Patient registries play an important role in obtaining real-world evidence of the cost-effectiveness of treatments. However, their implementation is costly and sometimes infeasible in many middle-income countries (MICs). We explored the combination of data-mining and a large claims database to estimate the direct healthcare costs of HER2-positive breast cancer (BC) treatment in Iran and the fracti...

Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer.

To monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC).

Paclitaxel reversed trastuzumab resistance via regulating JUN in human gastric cancer cells identified by FAN analysis.

In this study, we aim to use bioinformatics approach to identify paclitaxel-targeted modulators potentially involved in the process of reversing the trastuzumab resistance. Materials & methods: We extracted data from GSE77346 to identify potential trastuzumab resistance related genes, used bioinformatics analysis and functional/activity network approach to find genes involved in trastuzumab resis...

Role of MEL-18 Amplification in Anti-HER2 Therapy of Breast Cancer.

Resistance to HER2-targeted therapy with trastuzumab still remains a major challenge in HER2-amplified tumors. Here we investigated the potential role of MEL-18, a polycomb group gene, as a novel prognostic marker for trastuzumab resistance in HER2-positive (HER2+) breast cancer.

Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it.

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that accounts for up to 40% of all endometrial cancer-related deaths. Recent whole-exome sequencing studies have revealed HER2/neu amplification in 27-44% of USC patients, supporting HER2 as an attractive pathway for target therapies based on monoclonal antibodies or tyrosine kinase inhibitors. Preclinical studies and a ...

Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis.

Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast cancer (BC); however, we lack head-to-head pairwise assessment of survival or cardiotoxicity for specific combinations. We sought to identify optimal combinations.

Morpho-Functional Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells after Activation or Inhibition of Epidermal Growth Factor and Toll-Like Receptors or Treatment with DNA Intercalator Cisplatin.

This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our result...

Increasing HER2 α2,6 sialylation facilitates gastric cancer progression and resistance via the Akt and ERK pathways.

Upregulated β-galactoside α2,6-sialyltransferase I (ST6Gal-I) expression reportedly occurs in many cancers and is correlated with metastasis and poor prognosis. However, the mechanisms by which ST6Gal‑I facilitates gastric cancer progression remain poorly understood. Trastuzumab is exclusively used in human epidermal growth factor receptor 2 (HER2)+ gastric cancers; however, most advanced HE...

9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study.

Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment for HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The Short-HER study was aimed to assess the non-inferiority of 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy.

Heterogeneous distribution of trastuzumab in HER2-positive xenografts and metastases: role of the tumor microenvironment.

Most HER2-positive metastatic breast cancer patients continue to relapse. Incomplete access to all target HER2-positive cells in metastases and tumor tissues is a potential mechanism of resistance to trastuzumab. The location of locally bound trastuzumab was evaluated in HER2-positive tissues in vivo and as in vivo xenografts or metastases models in mice. Microenvironmental elements of tumors were...

Chemoenzymatic Defucosylation of Therapeutic Antibodies for Enhanced Effector Functions Using Bacterial α-Fucosidases.

Core fucosylation plays a critical role in modulating the effector functions of therapeutic antibodies such as the antibody-dependent cellular cytotoxicity (ADCC) through adversely affecting the affinity of antibodies for Fcγ receptors. Thus, a facile method for Fc defucosylation of antibodies is important both for functional studies and for an enhanced therapeutic efficacy. In this chapter, we d...

Prediction of postoperative disease-free survival and brain metastasis for HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab using a machine learning algorithm.

This study aimed to develop mathematical tools to predict the likelihood of recurrence after neoadjuvant chemotherapy (NAC) plus trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Peptide-directed photocrosslinking for site-specific conjugation of IgG.

Conjugation of antibody has expanded its applications in therapeutics and diagnostics, and various methods have been developed based on chemical or enzymatic reactions. However, majority of them have focused on synthetic molecules such as small molecules, nucleic acids, or synthetic materials, but site-specific conjugation of antibody with protein cargos has been rarely demonstrated so far. In thi...

Near infrared photoimmunotherapy using a fiber optic diffuser for treating peritoneal gastric cancer dissemination.

Peritoneal dissemination (PD) of abdominal malignancies is a common form of metastasis and its presence signals a poor prognosis. New treatment is required for patients with PD. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). In this study, we investigate in vitro and in vivo efficacy of trastuzumab (tra)-IR7...

tRNA-Derived Fragments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer.

Resistance to trastuzumab remains a common challenge to HER-2 positive breast cancer. Up until now, the underlying mechanism of trastuzumab resistance is still unclear. tRNA-derived small non-coding RNAs, a new class of small non-coding RNA (sncRNAs), have been observed to play an important role in cancer progression. However, the relationship between tRNA-derived fragments and trastuzumab resista...

T-DM1-resistant cells gain high invasive activity via EGFR and integrin cooperated pathways.

Ado-trastuzumab emtansine (Kadcyla®; T-DM1) is an antibody-drug conjugate developed to treat trastuzumab-resistant disease. Despite initial favorable outcomes, most patients eventually cease to respond due to developing acquired resistance to T-DM1. Currently, there is no targeted therapy to treat T-DM1-resistant disease. To explore novel therapeutic targets to improve therapeutic efficacy of T-D...

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