Abstract
Approximately 20-30% of breast cancers show increased expression of the HER2 receptor tyrosine kinase. Trastuzumab (Herceptin) is a clinically approved anti-HER2 monoclonal antibody. Many patients with HER2-overexpressing metastatic breast cancer respond to trastuzumab; however, a subset display primary drug resistance. In addition, many patients who initially respond to trastuzumab ultimately develop disease progression. Multiple molecular mechanisms contributing to trastuzumab resistance have been proposed in the literature. These mechanisms include cross-signaling from related HER/erbB receptors and compensatory signaling from receptors outside of the HER/erbB family, including receptors for insulin-like growth factor-I, vascular endothelial growth factor, and transforming growth factor beta. The major downstream signaling pathway activated by HER2 cross-talk is PI3K/mTOR, and a potential integrator of receptor cross-talk is Src-focal adhesion kinase (FAK) signaling. PI3K, Src, and FAK have independently been implicated in trastuzumab resistance. In this review, we will discuss pharmacological inhibition of HER2 cross-talk as a strategy to treat trastuzumab-refractory HER2-overexpresssing breast cancer.
Keywords: Breast cancer, erbB2, Her2, Herceptin, resistance, Trastuzumab, cross-talk, lapatinib, pertuzumab, IGF-IR, VEGF, TGF beta, FAK
Current Medicinal Chemistry
Title: Pharmacological Strategies to Overcome HER2 Cross-Talk and Trastuzumab Resistance
Volume: 19 Issue: 7
Author(s): R. Nahta
Affiliation:
Keywords: Breast cancer, erbB2, Her2, Herceptin, resistance, Trastuzumab, cross-talk, lapatinib, pertuzumab, IGF-IR, VEGF, TGF beta, FAK
Abstract: Approximately 20-30% of breast cancers show increased expression of the HER2 receptor tyrosine kinase. Trastuzumab (Herceptin) is a clinically approved anti-HER2 monoclonal antibody. Many patients with HER2-overexpressing metastatic breast cancer respond to trastuzumab; however, a subset display primary drug resistance. In addition, many patients who initially respond to trastuzumab ultimately develop disease progression. Multiple molecular mechanisms contributing to trastuzumab resistance have been proposed in the literature. These mechanisms include cross-signaling from related HER/erbB receptors and compensatory signaling from receptors outside of the HER/erbB family, including receptors for insulin-like growth factor-I, vascular endothelial growth factor, and transforming growth factor beta. The major downstream signaling pathway activated by HER2 cross-talk is PI3K/mTOR, and a potential integrator of receptor cross-talk is Src-focal adhesion kinase (FAK) signaling. PI3K, Src, and FAK have independently been implicated in trastuzumab resistance. In this review, we will discuss pharmacological inhibition of HER2 cross-talk as a strategy to treat trastuzumab-refractory HER2-overexpresssing breast cancer.
Export Options
About this article
Cite this article as:
Nahta R., Pharmacological Strategies to Overcome HER2 Cross-Talk and Trastuzumab Resistance, Current Medicinal Chemistry 2012; 19 (7) . https://dx.doi.org/10.2174/092986712799320691
DOI https://dx.doi.org/10.2174/092986712799320691 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pro-inflammatory Cytokines Modulate Glial Apolipoprotein E Secretion
Current Alzheimer Research Current Uses of Robotic Surgery for the Treatment of Benign Adnexal Conditions
Current Women`s Health Reviews Recent Nanocarrier Approaches for Targeted Drug Delivery in Cancer Therapy
Current Molecular Pharmacology Applications of Artificial Neural Networks in Medical Science
Current Clinical Pharmacology A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Body Mass Index, Lipid Metabolism and Estrogens: Their Impact on Coronary Heart Disease
Current Medicinal Chemistry miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets Imaging Drug Resistance with Radiolabeled Molecules
Current Pharmaceutical Design Subject Index to Volume 4
Current Drug Metabolism New Potential Pharmaceutical Applications of Hypericum Species
Mini-Reviews in Medicinal Chemistry Transient Expression of Chicken Antimicrobial Peptides by Mouse Mammary Carcinoma Cells C127
Protein & Peptide Letters Aflibercept (VEGF-TRAP): The Next Anti-VEGF Drug
Inflammation & Allergy - Drug Targets (Discontinued) Transcriptome Analysis of FEN1 Knockdown HEK293T Cell Strain Reveals Alteration in Nucleic Acid Metabolism, Virus Infection, Cell Morphogenesis and Cancer Development
Combinatorial Chemistry & High Throughput Screening Therapeutic Rationale for mTOR Inhibition in Advanced Renal Cell Carcinoma
Current Clinical Pharmacology Cytotoxicity and Anti-Inflammatory Effects of Polyherbal Formulations, Joint Pain Spl and Rumalaya Forte on Lipopolysaccharide Induced Inflammation in IC-21 Macrophages
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Zebrafish as a Model System to Screen Radiation Modifiers
Current Genomics Chondroitin Sulphate Decorated Polymeric Nanoparticles: An Effective Carrier for Enhancement of Lung Cancer Targeting Capabilities of Anticancer Drug
Current Nanomedicine Glucagon and Glucagon-Like Peptide Receptors as Drug Targets
Current Pharmaceutical Design Preclinical Analyses of the Therapeutic Potential of Allopregnanolone to Promote Neurogenesis In Vitro and In Vivo in Transgenic Mouse Model of Alzheimers Disease
Current Alzheimer Research PP2A in the Regulation of Cell Motility and Invasion
Current Protein & Peptide Science