We are analyzing https://link.springer.com/article/10.1186/s13058-014-0419-5.

Title:
Dual HER2 blockade: preclinical and clinical data | Breast Cancer Research
Description:
The estrogen receptor and human epidermal growth factor receptor (HER) signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. Not surprisingly, targeting these pathways provides the most effective therapies in appropriately selected patients. However, de novo and acquired resistance remain major obstacles to successful treatment. By increasing the understanding of the molecular mechanisms of combined HER2-targeted therapies, we aim to be better able to select patients who would respond to these treatments and understand some of the mechanisms of resistance to HER2-targeted treatments. Recent studies have demonstrated an increased effectiveness of dual targeted HER2 therapies against HER2-amplified breast cancer as compared with single blockade. These studies have resulted in the recent US Food and Drug Administration approval of the combination of taxane chemotherapy with pertuzumab and trastuzumab in the first-line metastatic setting as well as an accelerated approval in the neoadjuvant setting. Another mechanism for overcoming resistance to HER2 targeted therapies is the antibody-drug conjugate trastuzumab-emtansine, which targets the HER2 receptor conjugated to the potent antimicrotubule agent mertansine, allowing for intracellular release of the cytotoxic drug. Studies evaluating the efficacy of dual blockade with antibody-drug conjugate are currently ongoing. This article reviews recent data on different combinations of anti-HER2 treatments as well as ongoing and future research in this area.
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Keywords {🔍}

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Topics {✒️}

mitogen-activated protein kinase gov/newsevents/newsroom/pressannouncements/ucm370393 perez & gerardo colon-otero early-stage breast cancer single-agent her2-targeted therapies her2-positive breast cancers her2-positive locally advanced hormone receptor-positive subsets antibody-drug conjugate trastuzumab-emtansine hormone receptor-negative subsets her2-positive breast cancer her2-amplified breast cancer human breast cancers hormone receptor-positive tumors her2-targeted antitumor properties hormone receptor-negative tumors optimal anti-her2 therapy hormone receptor-positive patients combined her2-targeted therapies mcf7/her2-18 xenograft model microtubule-inhibitory agent mertansine her2-positive mbc showed //breast-cancer-research article download pdf dual her2-targeted treatments improves disease-free survival hormone receptor-positive lapatinib 750 mg/daily orally inhibits her2-trastuzumab interactions single-agent her2 blockade receptor targeted therapies her2-her3 heterodimers leads tyrosine kinase inhibitor advanced breast cancer multiple targeted therapies akt/protein kinase her2-positive cancer approved her2-targeted drugs tumor volume fold-change placebo versus t-dm1 single-agent neratinib showed her2 targeted therapies her2 tyrosine kinase compares single-agent trastuzumab her2-overexpressing cells tumor growth resumed dual targeted therapies anti-her2 therapies single-agent treatment group single-agent t-dm1

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Schema {🗺️}

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         headline:Dual HER2 blockade: preclinical and clinical data
         description:The estrogen receptor and human epidermal growth factor receptor (HER) signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. Not surprisingly, targeting these pathways provides the most effective therapies in appropriately selected patients. However, de novo and acquired resistance remain major obstacles to successful treatment. By increasing the understanding of the molecular mechanisms of combined HER2-targeted therapies, we aim to be better able to select patients who would respond to these treatments and understand some of the mechanisms of resistance to HER2-targeted treatments. Recent studies have demonstrated an increased effectiveness of dual targeted HER2 therapies against HER2-amplified breast cancer as compared with single blockade. These studies have resulted in the recent US Food and Drug Administration approval of the combination of taxane chemotherapy with pertuzumab and trastuzumab in the first-line metastatic setting as well as an accelerated approval in the neoadjuvant setting. Another mechanism for overcoming resistance to HER2 targeted therapies is the antibody-drug conjugate trastuzumab-emtansine, which targets the HER2 receptor conjugated to the potent antimicrotubule agent mertansine, allowing for intracellular release of the cytotoxic drug. Studies evaluating the efficacy of dual blockade with antibody-drug conjugate are currently ongoing. This article reviews recent data on different combinations of anti-HER2 treatments as well as ongoing and future research in this area.
         datePublished:2014-07-31T00:00:00Z
         dateModified:2014-07-31T00:00:00Z
         pageStart:1
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      headline:Dual HER2 blockade: preclinical and clinical data
      description:The estrogen receptor and human epidermal growth factor receptor (HER) signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. Not surprisingly, targeting these pathways provides the most effective therapies in appropriately selected patients. However, de novo and acquired resistance remain major obstacles to successful treatment. By increasing the understanding of the molecular mechanisms of combined HER2-targeted therapies, we aim to be better able to select patients who would respond to these treatments and understand some of the mechanisms of resistance to HER2-targeted treatments. Recent studies have demonstrated an increased effectiveness of dual targeted HER2 therapies against HER2-amplified breast cancer as compared with single blockade. These studies have resulted in the recent US Food and Drug Administration approval of the combination of taxane chemotherapy with pertuzumab and trastuzumab in the first-line metastatic setting as well as an accelerated approval in the neoadjuvant setting. Another mechanism for overcoming resistance to HER2 targeted therapies is the antibody-drug conjugate trastuzumab-emtansine, which targets the HER2 receptor conjugated to the potent antimicrotubule agent mertansine, allowing for intracellular release of the cytotoxic drug. Studies evaluating the efficacy of dual blockade with antibody-drug conjugate are currently ongoing. This article reviews recent data on different combinations of anti-HER2 treatments as well as ongoing and future research in this area.
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      dateModified:2014-07-31T00:00:00Z
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         Overall Survival
         Trastuzumab
         Human Epidermal Growth Factor Receptor
         Lapatinib
         Pertuzumab
         Cancer Research
         Oncology
         Surgical Oncology
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         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fs13058-014-0419-5/MediaObjects/13058_2014_419_Fig1_HTML.jpg
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               name:Department of Medicine, Weill Cornell Medical College, New York, USA
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      name:Department of Medicine, Weill Cornell Medical College, New York, USA
      name:Division of Hemotology and Oncology, College of Medicine, Mayo Clinic, Jacksonville, USA
      name:Division of Hemotology and Oncology, College of Medicine, Mayo Clinic, Jacksonville, USA

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