Abstract
Deregulated activation of protein tyrosine kinases (PTKs) is a frequent event underlying malignant transformation in many types of cancer. The formation of oncogenic fusion tyrosine kinases (FTKs) resulting from genomic rearrangements, represents a common mechanism by which kinases escape the strict controls that normally regulate their expression and activation. FTKs are typically composed of an N-terminal dimerisation domain, provided by the fusion partner protein, fused to the kinase domain of receptor or nonreceptor tyrosine kinases (non-RTKs). Since FTKs do not contain extracellular domains, they share many characteristics with non-RTKs in terms of their properties and approaches for therapeutic targeting. FTKs are cytoplasmic or sometimes nuclear proteins, depending on the normal distribution of their fusion partner. FTKs no longer respond to ligand and are instead constitutively activated by dimerisation induced by the fusion partner. Unlike RTKs, FTKs cannot be targeted by therapeutic antibodies, instead they require agents that can cross the cell membrane as with non-RTKs. Here we review the PTKs known to be expressed as FTKs in cancer and the strategies for molecularly targeting these FTKs in anti-cancer therapy.
Keywords: Oncogenic fusion proteins, anti-cancer therapy, tyrosine kinase, small molecule inhibitors
Anti-Cancer Agents in Medicinal Chemistry
Title: Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Volume: 7 Issue: 6
Author(s): Rosalind H. Gunby, Elisa Sala, Carmen J. Tartari, Miriam Puttini, Carlo Gambacorti-Passerini and Luca Mologni
Affiliation:
Keywords: Oncogenic fusion proteins, anti-cancer therapy, tyrosine kinase, small molecule inhibitors
Abstract: Deregulated activation of protein tyrosine kinases (PTKs) is a frequent event underlying malignant transformation in many types of cancer. The formation of oncogenic fusion tyrosine kinases (FTKs) resulting from genomic rearrangements, represents a common mechanism by which kinases escape the strict controls that normally regulate their expression and activation. FTKs are typically composed of an N-terminal dimerisation domain, provided by the fusion partner protein, fused to the kinase domain of receptor or nonreceptor tyrosine kinases (non-RTKs). Since FTKs do not contain extracellular domains, they share many characteristics with non-RTKs in terms of their properties and approaches for therapeutic targeting. FTKs are cytoplasmic or sometimes nuclear proteins, depending on the normal distribution of their fusion partner. FTKs no longer respond to ligand and are instead constitutively activated by dimerisation induced by the fusion partner. Unlike RTKs, FTKs cannot be targeted by therapeutic antibodies, instead they require agents that can cross the cell membrane as with non-RTKs. Here we review the PTKs known to be expressed as FTKs in cancer and the strategies for molecularly targeting these FTKs in anti-cancer therapy.
Export Options
About this article
Cite this article as:
Gunby H. Rosalind, Sala Elisa, Tartari J. Carmen, Puttini Miriam, Gambacorti-Passerini Carlo and Mologni Luca, Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (6) . https://dx.doi.org/10.2174/187152007784111340
DOI https://dx.doi.org/10.2174/187152007784111340 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Cardiovascular Disease in Juvenile Idiopathic Arthritis
Current Vascular Pharmacology PPARγ Activation Improves the Molecular and Functional Components of Ito Remodeling by Angiotensin II
Current Pharmaceutical Design GCPII Variants, Paralogs and Orthologs
Current Medicinal Chemistry Cutaneous Metabolism in Transdermal Drug Delivery
Current Drug Metabolism The Brain, the Penis and Steroid Hormones: Clinical Correlates with Endothelial Dysfunction
Current Pharmaceutical Design Thiazolidinediones and Type 2 Diabetes: From Cellular Targets to Cardiovascular Benefit
Current Drug Targets Flexible Bronchoscopy Biopsy Tools and Techniques to Optimize Diagnostic Yield: A Contemporary Review
Current Respiratory Medicine Reviews Drug Targets in Infections with Ebola and Marburg Viruses
Infectious Disorders - Drug Targets Development of Infection and Inflammation Targeting Compounds
Current Radiopharmaceuticals The Role of Infections in the Pathogenesis of Autoimmune Diseases
Current Drug Targets - Inflammation & Allergy Haemostatic Activation in HIV Infected Patients Treated with Different Antiretroviral Regimens
Current HIV Research Glial Reaction in Parkinsons Diseases: Inflammatory Activation Signaling of Glia as a Potential Therapeutic Target
Current Signal Transduction Therapy Therapeutic Angiogenesis: Recent and Future Prospects of Gene Therapy in Peripheral Artery Disease
Current Gene Therapy The S100A8 and S100A9 Proteins are Attractive Targets to Modulate Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Postoperative Care of the Transplanted Patient
Current Cardiology Reviews Targeting Potassium Channels: New Advances in Cardiovascular Therapy
Recent Patents on Cardiovascular Drug Discovery Common and Uncommon Features of Rheumatoid Arthritis and Chronic Obstructive Pulmonary Disease: Clues to a Future Therapy
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Near Infrared Spectroscopy in Healthy Preterm and Term Newborns: Correlation with Gestational Age and Standard Monitoring Parameters
Current Neurovascular Research Endothelial Dysfunction in Cardiac Allograft Vasculopathy: Potential Pharmacological Interventions
Current Vascular Pharmacology miR-27b-3p is Highly Expressed in Serum of Patients with Preeclampsia and has Clinical Significance
Endocrine, Metabolic & Immune Disorders - Drug Targets