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Herceptin (Trastuzumab) Research

03:00 EST 15th December 2018 | BioPortfolio

HER2 signaling regulates the tumor immune microenvironment and trastuzumab efficacy.

Through whole-transcriptome profiling of HER2+ breast carcinomas (BCs), we previously showed that those sensitive to trastuzumab are addicted to this oncoprotein and are enriched in immune pathways, raising the hypothesis that HER2 itself regulates immune cell recruitment. In the present study we investigated the relationship between HER2 activity and the pro-trastuzumab tumor immune milieu. Gene...

Evaluation of the prognostic value of all four HER family receptors in patients with metastatic breast cancer treated with trastuzumab: A Hellenic Cooperative Oncology Group (HeCOG) study.

In the current study, we performed a complete analysis, with four different methods, of all four HER family receptors, in a series of patients with metastatic breast cancer treated with trastuzumab-based regimens and evaluated their prognostic value. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 227 patients, considered to be HER2-positive when assessed at the local lab...

Hydrogels with prolonged release of therapeutic antibody: Block junction chemistry modification of 'ABA' copolymers provides superior anticancer efficacy.

In this study, we report a new series of vitamin E-functionalized 'ABA' triblock copolymers with carbamate block junction, which can form hydrogen-bonds. These polymers were synthesized via solvent- and catalyst-free nucleophilic addition between PEG-diamine and vitamin E-functionalized cyclic carbonate. The catalyst-free synthesis enabled an easy purification step and recycling of excess monomers...

HER2-targeted therapy: an emerging strategy in advanced colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors; it is a focus of research globally, but the identification of clinically actionable oncogenic drivers remains elusive. HER2 activation is present in approximately 5% of CRC and has acquired resistance to EGFR-targeted therapy. Early clinical trials suggest an emerging role for personalized HER2-targeted therapy in a subset of meta...

Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer.

The purpose of this study is to investigate imaging and histology-based measurements of intratumoral heterogeneity to evaluate early treatment response to targeted therapy in a murine model of HER2+ breast cancer. BT474 tumor-bearing mice (N = 30) were treated with trastuzumab or saline and imaged longitudinally with either dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) or F-fluo...

From Research to Policy Implementation: Trastuzumab in Early-Stage Breast Cancer Treatment in Thailand.

To evaluate the adjuvant therapy of trastuzumab cost and quality-adjusted life-years (QALYs) in lifetime horizon and describe the use of an economic evaluation in supporting policy-making decisions in the treatment of early-stage breast cancer in Thailand.

Extramedullary Haematopoiesis in Axillary Lymph Nodes of Breast Carcinoma Patients Receiving Neoadjuvant Chemotherapy: A Potential Diagnostic Pitfall.

Extramedullary haematopoiesis (EMH) in the axillary lymph node of breast cancer patients is extremely rare but when encountered can represent a diagnostic challenge. We aim to highlight this incidental finding as a diagnostic pitfall which can be mistaken for metastatic carcinoma (particularly of the metaplastic type). We report the case of a 68-year-old Caucasian female with a family history of c...

Targeting 17q23 amplicon to overcome the resistance to anti-HER2 therapy in HER2+ breast cancer.

Chromosome 17q23 amplification occurs in ~11% of human breast cancers. Enriched in HER2+ breast cancers, the 17q23 amplification is significantly correlated with poor clinical outcomes. In addition to the previously identified oncogene WIP1, we uncover an oncogenic microRNA gene, MIR21, in a majority of the WIP1-containing 17q23 amplicons. The 17q23 amplification results in aberrant expression of...

A multicenter REtrospective observational study of first-line treatment with PERtuzumab, trastuzumab and taxanes for advanced HER2 positive breast cancer patients. RePer Study.

We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance wer...

Safety profile of subcutaneous trastuzumab for the treatment of patients with HER2-positive early or locally advanced breast cancer: primary analysis of the SCHEARLY study.

Subcutaneous trastuzumab (H SC) is a valuable alternative to the intravenous formulation. This study assessed H SC safety and tolerability in human epidermal growth factor receptor 2 (HER2)+ early/locally advanced breast cancer (EBC/LABC).

Prolonged In-use Stability of Reconstituted Herceptin in Commercial Intravenous Bags.

Herceptin is a humanized monoclonal antibody that selectively binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2). Herceptin has an important role in the treatment of HER2-positive breast cancer when used in the neoadjuvant, adjuvant, and metastatic settings, and in the treatment of HER2-positive metastatic gastric cancer, and gastroesophageal junction adenocarcino...

The incidence of atrial fibrillation with Trastuzumab treatment: a systematic review and meta-analysis.

Cases of cardiotoxicity related to trastuzumab have been reported. This systematic review and meta-analysis evaluated the risk of atrial fibrillation (AF) in patients of breast cancer treated with trastuzumab.

Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer.

Combined anthracycline-trastuzumab chemotherapy has been associated with LV dysfunction. We aimed to assess early changes in left ventricular (LV) and right ventricular (RV) mechanics associated with combined anthracycline-trastuzumab treatment for breast cancer. As well as explore whether early changes in 2-dimensional (2D)-speckle tracking echocardiography (STE) could predict later chemotherapy-...

Monitoring Src status after dasatinib treatment in HER2+ breast cancer with Zr-trastuzumab PET imaging.

De novo or acquired resistance in breast cancer leads to treatment failures and disease progression. In human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer, Src, a non-receptor tyrosine kinase, is identified as a major mechanism of trastuzumab resistance, with its activation stabilizing aberrant HER2 signaling, thus making it an attractive target for inhibition. Here, we...

Comprehensive Preclinical Pharmacokinetic Evaluations of Trastuzumab Deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in Cynomolgus Monkeys.

1. Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8. Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species. 2. Following intravenous...

Evaluation of the Insulin-like Growth Factor Receptor Pathway in Patients with Advanced Breast Cancer Treated with Trastuzumab.

Trastuzumab is a monoclonal antibody against HER2-positive breast cancer. Despite improving the natural history of the disease, there is a number of patients who are resistant to it, whereas all patients will eventually develop resistance and disease will progress. Inconsistent preclinical data show that the IGF-R pathway may contribute to either de novo or acquired resistance to trastuzumab.

Successful intracranial delivery of trastuzumab by gene-therapy for treatment of HER2-positive breast cancer brain metastases.

Trastuzumab is a monoclonal antibody which demonstrates efficacy for HER2 positive breast cancer patients. Recently, an increased incidence of brain metastasis in trastuzumab-treated patients has been reported. The reason for this may be the effectiveness of systemic trastuzumab allowing patients to survive longer thus providing time for brain metastases to develop, along with the lack of penetrat...

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 ...

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