Abstract
Fibroblast growth factors (FGF) and their tyrosine kinase receptors (FGFR) support cell proliferation, survival and migration during embryonic development, organogenesis and tissue maintenance and their deregulation is frequently observed in cancer development and progression. Consequently, increasing efforts are focusing on the development of strategies to target FGF/FGFR signaling for cancer therapy.
Among the FGFRs the family member FGFR4 is least well understood and differs from FGFRs1-3 in several aspects. Importantly, FGFR4 deletion does not lead to an embryonic lethal phenotype suggesting the possibility that its inhibition in cancer therapy might not cause grave adverse effects. In addition, the FGFR4 kinase domain differs sufficiently from those of FGFRs1-3 to permit development of highly specific inhibitors. The oncogenic impact of FGFR4, however, is not undisputed, as the FGFR4-mediated hormonal effects of several FGF ligands may also constitute a tissue-protective tumor suppressor activity especially in the liver.
Therefore it is the purpose of this review to summarize all relevant aspects of FGFR4 physiology and pathophysiology and discuss the options of targeting this receptor for cancer therapy.
Keywords: FGFR4, targeted therapy.
Current Pharmaceutical Design
Title:Is Fibroblast Growth Factor Receptor 4 a Suitable Target of Cancer Therapy?
Volume: 20 Issue: 17
Author(s): Christine Heinzle, Zeynep Erdem, Jakob Paur, Bettina Grasl-Kraupp, Klaus Holzmann, Michael Grusch, Walter Berger and Brigitte Marian
Affiliation:
Keywords: FGFR4, targeted therapy.
Abstract: Fibroblast growth factors (FGF) and their tyrosine kinase receptors (FGFR) support cell proliferation, survival and migration during embryonic development, organogenesis and tissue maintenance and their deregulation is frequently observed in cancer development and progression. Consequently, increasing efforts are focusing on the development of strategies to target FGF/FGFR signaling for cancer therapy.
Among the FGFRs the family member FGFR4 is least well understood and differs from FGFRs1-3 in several aspects. Importantly, FGFR4 deletion does not lead to an embryonic lethal phenotype suggesting the possibility that its inhibition in cancer therapy might not cause grave adverse effects. In addition, the FGFR4 kinase domain differs sufficiently from those of FGFRs1-3 to permit development of highly specific inhibitors. The oncogenic impact of FGFR4, however, is not undisputed, as the FGFR4-mediated hormonal effects of several FGF ligands may also constitute a tissue-protective tumor suppressor activity especially in the liver.
Therefore it is the purpose of this review to summarize all relevant aspects of FGFR4 physiology and pathophysiology and discuss the options of targeting this receptor for cancer therapy.
Export Options
About this article
Cite this article as:
Heinzle Christine, Erdem Zeynep, Paur Jakob, Grasl-Kraupp Bettina, Holzmann Klaus, Grusch Michael, Berger Walter and Marian Brigitte, Is Fibroblast Growth Factor Receptor 4 a Suitable Target of Cancer Therapy?, Current Pharmaceutical Design 2014; 20 (17) . https://dx.doi.org/10.2174/13816128113199990594
DOI https://dx.doi.org/10.2174/13816128113199990594 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Apoptosis Induction by Erucylphosphohomocholine via the 18 kDa Mitochondrial Translocator Protein: Implications for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes
Anti-Cancer Agents in Medicinal Chemistry Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Systemic Approach to the Study of Complex Bone Disorders at the Whole- Genome Level
Current Genomics Anticancer Properties of Flavonoids: Roles in Various Stages of Carcinogenesis
Cardiovascular & Hematological Agents in Medicinal Chemistry Relevance of the Deletion Polymorphisms of the Glutathione S-Transferases GSTT1 and GSTM1 in Pharmacology and Toxicology
Current Drug Metabolism Molecular Mechanism of Anti-tumor Effect by Triptolide in Hematological Malignancies
Current Signal Transduction Therapy Molecular Pathogenesis of Non Muscle-Invasive Bladder Cancer: Implications for Novel Targeted Therapies
Current Molecular Medicine Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO)
Current Radiopharmaceuticals Effect of two Antiandrogens as Protectors of Prostate and Brain in a Huntington`s Animal Model
Anti-Cancer Agents in Medicinal Chemistry The Synthesis of Chalcones as Anticancer Prodrugs and their Bioactivation in CYP1 Expressing Breast Cancer Cells
Medicinal Chemistry Non Smoking for Successful Aging: Therapeutic Perspectives
Current Pharmaceutical Design Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism Competition Between Tumor and Mononuclear Phagocyte System Causing the Low Tumor Distribution of Nanoparticles and Strategies to Improve Tumor Accumulation
Current Drug Delivery Recent Patents on Morphometric Analysis of Eukaryotic Cells
Recent Patents on Medical Imaging Recent Patents on Light Based Therapies: Photodynamic Therapy, Photothermal Therapy and Photoimmunotherapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Organic Synthesis and Antisense Effects of Oligonucleotide-Peptide Conjugates
Current Organic Chemistry Molecules to Selectively Target Receptors for Treatment of Pain and Neurogenic Inflammation
Recent Patents on Inflammation & Allergy Drug Discovery Tumor Specific Imaging Using Tc-99m and Ga-68 Labeled Radiopharmaceuticals
Current Medical Imaging DNA Drug Design for Cancer Therapy
Current Pharmaceutical Design