Abstract
Background: Molecular lesions of the NRG1 gene were recently described as a new molecular feature of Invasive Mucinous Adenocarcinoma of the lung. The NRG1 chimeric ligand leads to aberrant activation of the ErbB2/ErbB3 signaling via PI3K–AKT and MAPK cellular cascades. This review aims to highlight the current knowledge about the ErbB network and the effect of NRG1 deregulation in lung cancer and their merger into the ErbB/PI3K-AKT axis modulation by current pharmacologic strategies.
Methods: We performed a structured search of bibliographic databases for peer-reviewed literature to outline the state of the art with regard ErbB signaling deregulation and NRG1 function in lung cancer. The quality of retrieved papers was assessed using standard tools and one hundred thirty-five were included in the review. In many papers the molecular lesions affecting the ErbB receptors in lung cancer but also in other type of solid tumors were updated. Papers describing the physiological role of NRG1 in cells was also screened for the review preparation, as well as the paper reporting NRG1 fusions in lung cancer and their implication in aberrant ErbB pathway activation.
Results and Conclusion: Overall, this review highpoints how the knowledge of new molecular mechanisms of ErbB pathway deregulation may help in gaining new insights into the molecular status of lung cancer patients and unveil a novel molecular markers of patients' stratification. Moreover, this ultimately led the selection of new compounds designed to inhibit the bound between Nrg1-ErbB3 as a good alternative way to block the ErbB intracellular signaling.
Keywords: ErbB network, ErbB3, NRG1 fusion, lung cancer, target therapy, resistance to therapy.
Current Medicinal Chemistry
Title:NRG1-ErbB Lost in Translation: A New Paradigm for Lung Cancer?
Volume: 24 Issue: 38
Author(s): Domenico Trombetta, Antonio Rossi, Federico P. Fabrizio, A. Sparaneo , Paolo Graziano, Vito M. Fazio and Lucia A. Muscarella*
Affiliation:
- Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG),Italy
Keywords: ErbB network, ErbB3, NRG1 fusion, lung cancer, target therapy, resistance to therapy.
Abstract: Background: Molecular lesions of the NRG1 gene were recently described as a new molecular feature of Invasive Mucinous Adenocarcinoma of the lung. The NRG1 chimeric ligand leads to aberrant activation of the ErbB2/ErbB3 signaling via PI3K–AKT and MAPK cellular cascades. This review aims to highlight the current knowledge about the ErbB network and the effect of NRG1 deregulation in lung cancer and their merger into the ErbB/PI3K-AKT axis modulation by current pharmacologic strategies.
Methods: We performed a structured search of bibliographic databases for peer-reviewed literature to outline the state of the art with regard ErbB signaling deregulation and NRG1 function in lung cancer. The quality of retrieved papers was assessed using standard tools and one hundred thirty-five were included in the review. In many papers the molecular lesions affecting the ErbB receptors in lung cancer but also in other type of solid tumors were updated. Papers describing the physiological role of NRG1 in cells was also screened for the review preparation, as well as the paper reporting NRG1 fusions in lung cancer and their implication in aberrant ErbB pathway activation.
Results and Conclusion: Overall, this review highpoints how the knowledge of new molecular mechanisms of ErbB pathway deregulation may help in gaining new insights into the molecular status of lung cancer patients and unveil a novel molecular markers of patients' stratification. Moreover, this ultimately led the selection of new compounds designed to inhibit the bound between Nrg1-ErbB3 as a good alternative way to block the ErbB intracellular signaling.
Export Options
About this article
Cite this article as:
Trombetta Domenico , Rossi Antonio , Fabrizio P. Federico , Sparaneo A., Graziano Paolo , Fazio M. Vito and Muscarella A. Lucia*, NRG1-ErbB Lost in Translation: A New Paradigm for Lung Cancer?, Current Medicinal Chemistry 2017; 24 (38) . https://dx.doi.org/10.2174/0929867324666170911170554
DOI https://dx.doi.org/10.2174/0929867324666170911170554 |
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
-
Status of Bi- and Multi-Nuclear Platinum Anticancer Drug Development
Anti-Cancer Agents in Medicinal Chemistry Perspectives in Breast and Ovarian Cancer Chemotherapy by Nanomedicine Approach: Nanoformulations in Clinical Research
Current Medicinal Chemistry Glycerophospholipid Synthesis as a Novel Drug Target Against Cancer
Current Molecular Pharmacology Cetuximab, A Chimeric Anti-Epidermal Growth Factor Receptor Monoclonal Antibody, in Colorectal Cancer Treatment
Current Cancer Therapy Reviews Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?
Current Cancer Drug Targets Hypoxia-Inducible Factor (HIF): Fuel for Cancer Progression
Current Molecular Pharmacology The Research Progress of Taxol in <i>Taxus</i>
Current Pharmaceutical Biotechnology Medicinal Plants from Peru: A Review of Plants as Potential Agents Against Cancer
Anti-Cancer Agents in Medicinal Chemistry Autophagy Driven Extracellular Vesicles in the Leukaemic Microenvironment
Current Cancer Drug Targets ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development
Current Pharmaceutical Design Neuropilin and Neuropilin Associated Molecules as New Molecular Targets in Pancreatic Adenocarcinoma
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in the Research and Development of B-Raf Inhibitors
Current Medicinal Chemistry Recent Advances in the Diagnosis and Therapy of Primary Adrenal Insufficiency
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents TLR7/9 Antagonists as Therapeutics for Immune-Mediated Inflammatory Disorders
Inflammation & Allergy - Drug Targets (Discontinued) Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Molecular Modeling and Medicinal Chemistry Aspects of Phospho-Glycoprotein&#
Current Drug Metabolism Molecular Mechanisms Responsible for <i>In Vitro</i> Cytotoxic Attributes of <i>Conyza bonariensis</i> Extract against Lymphoblastic Leukaemia Jurkat Cells
Anti-Cancer Agents in Medicinal Chemistry Synthesis, DNA Binding Ability and Anticancer Activity of 2-heteroaryl Substituted Benzimidazoles Linked Pyrrolo[2,1-c][1,4]benzodiazepine Conjugates
Medicinal Chemistry Phytochemicals: Key to Effective Anticancer Drugs
Mini-Reviews in Organic Chemistry Structure Activity Relationship of Arylidene Pyrrolo and Pyrido [2,1-b] Quinazolones as Cytotoxic Agents: Synthesis, SAR Studies, Biological Evaluation and Docking Studies
Medicinal Chemistry