Abstract
The old-fashioned anticancer approaches, aiming at arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual singletarget drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of a multi-target approach, the closely related evolutionary members of the tyrosine kinase family are ideal candidates. Indeed, tyrosine kinase activities are not only critical in tumor phenotype maintenance, but also modulate several functions in the tumor microenvironment. Consequently, several multikinase inhibitors were approved in the last decade, and many new molecules are currently in preclinical or clinical development. In the present review we report on the most widely FDA-approved multitargeted drugs, discussing about their mechanism of action and outlining the clinical trials that have brought them to approval.
Keywords: Multitargeted drugs, anticancer agents, polypharmacology, tyrosine kinase receptors, oncogene addiction, tumor microenvironment, FDA-approved drugs.
Current Medicinal Chemistry
Title:Kinase Inhibitors in Multitargeted Cancer Therapy
Volume: 24 Issue: 16
Author(s): Carla Gentile, Annamaria Martorana, Antonino Lauria*Riccardo Bonsignore
Affiliation:
- Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche “STEBICEF” - Università di Palermo, Viale delle Scienze - Ed. 17 -90128 Palermo,Italy
Keywords: Multitargeted drugs, anticancer agents, polypharmacology, tyrosine kinase receptors, oncogene addiction, tumor microenvironment, FDA-approved drugs.
Abstract: The old-fashioned anticancer approaches, aiming at arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual singletarget drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of a multi-target approach, the closely related evolutionary members of the tyrosine kinase family are ideal candidates. Indeed, tyrosine kinase activities are not only critical in tumor phenotype maintenance, but also modulate several functions in the tumor microenvironment. Consequently, several multikinase inhibitors were approved in the last decade, and many new molecules are currently in preclinical or clinical development. In the present review we report on the most widely FDA-approved multitargeted drugs, discussing about their mechanism of action and outlining the clinical trials that have brought them to approval.
Export Options
About this article
Cite this article as:
Gentile Carla, Martorana Annamaria, Lauria Antonino*, Bonsignore Riccardo, Kinase Inhibitors in Multitargeted Cancer Therapy, Current Medicinal Chemistry 2017; 24 (16) . https://dx.doi.org/10.2174/0929867324666170112112734
DOI https://dx.doi.org/10.2174/0929867324666170112112734 |
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
-
Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral Alterations Including Autistic Behavior
Current Genomics The Relationship between Ferroptosis and Tumors: A Novel Landscape for Therapeutic Approach
Current Gene Therapy Intersection of MicroRNA and Gene Regulatory Networks and their Implication in Cancer
Current Pharmaceutical Biotechnology Reposition of the Fungicide Ciclopirox for Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Autophagy in Diabetic Retinopathy
Current Neuropharmacology Contrast-enhanced Ultrasound for Liver Imaging: Recent Advances
Current Pharmaceutical Design Chemical and Clinical Development of Darinaparsin, a Novel Organic Arsenic Derivative
Anti-Cancer Agents in Medicinal Chemistry The Potential Health Benefits of Algae and Micro Algae in Medicine: A Review on Spirulina platensis
Current Nutrition & Food Science Morphologic and Molecular Backgrounds for Personalized Management of Genito-Urinary Cancers: An Overview
Current Drug Targets Graphene and Graphene Oxide as a Docking Station for Modern Drug Delivery System
Current Drug Delivery Methylation Profile of miR-9-1 and miR-9-1/-9-3 as Potential Biomarkers of Diabetic Retinopathy
Current Diabetes Reviews Beyond Promoter: The Role of Macrophage in Invasion and Progression of Renal Cell Carcinoma
Current Stem Cell Research & Therapy Green Synthesis of Silver Nanocomposites of Nigella sativa Seeds Extract for Hepatocellular Carcinoma
Current Nanomaterials Pharmacoepigenomics: An Interplay of Epigenetic Modulation of Drug Response and Modulation of the Epigenome by Drugs
Current Pharmaceutical Design TNF-Related Apoptosis-Inducing Ligand (TRAIL): A Potential Candidate for Combined Treatment of Hematological Malignancies
Current Pharmaceutical Design Risk for Cervical Intraepithelial Neoplasia in Systemic Lupus Erythematosus is not Related to Disease Severity
Current Rheumatology Reviews Polymer-dendrimer Hybrids as Carriers of Anticancer Agents
Current Drug Targets Modulation of the Immune Response by Targeting Endothelial Cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Inflammatory Mediators Hold the Key to Dendritic Cell Suppression and Tumor Progression
Current Medicinal Chemistry Beneficial Actions of Polyunsaturated Fatty Acids in Cardiovascular Diseases: But, How and Why?
Current Nutrition & Food Science