Abstract
Targeted therapies by means of compounds that inhibit a specific target molecule represent a new perspective in the treatment of cancer. In contrast to conventional chemotherapy which acts on all dividing cells generating toxic effects and damage of normal tissues, targeted drugs allow to hit, in a more specific manner, subpopulations of cells directly involved in tumor progression. Molecules controlling cell proliferation and death, such as Tyrosine Kinase Receptors (RTKs) for growth factors, are among the best targets for this type of therapeutic approach. Two classes of compounds targeting RTKs are currently used in clinical practice: monoclonal antibodies and tyrosine kinase inhibitors. The era of targeted therapy began with the approval of Trastuzumab, a monoclonal antibody against HER2, for treatment of metastatic breast cancer, and Imatinib, a small tyrosine kinase inhibitor targeting BCR-Abl, in Chronic Myeloid Leukemia. Despite the initial enthusiasm for the efficacy of these treatments, clinicians had to face soon the problem of relapse, as almost invariably cancer patients developed drug resistance, often due to the activation of alternative RTKs pathways. In this view, the rationale at the basis of targeting drugs is radically shifting. In the past, the main effort was aimed at developing highly specific inhibitors acting on single RTKs. Now, there is a general agreement that molecules interfering simultaneously with multiple RTKs might be more effective than single target agents. With the recent approval by FDA of Sorafenib and Sunitinib - targeting VEGFR, PDGFR, FLT-3 and c-Kit - a different scenario has been emerging, where a new generation of anti-cancer drugs, able to inhibit more than one pathway, would probably play a major role.
Keywords: Tyrosine kinase receptors, monoclonal antibodies, small molecules, tyrosine kinase inhibitors, targeted therapy, cancer therapy
Current Medicinal Chemistry
Title: From Single- to Multi-Target Drugs in Cancer Therapy: When Aspecificity Becomes an Advantage
Volume: 15 Issue: 5
Author(s): S. Giordano and A. Petrelli
Affiliation:
Keywords: Tyrosine kinase receptors, monoclonal antibodies, small molecules, tyrosine kinase inhibitors, targeted therapy, cancer therapy
Abstract: Targeted therapies by means of compounds that inhibit a specific target molecule represent a new perspective in the treatment of cancer. In contrast to conventional chemotherapy which acts on all dividing cells generating toxic effects and damage of normal tissues, targeted drugs allow to hit, in a more specific manner, subpopulations of cells directly involved in tumor progression. Molecules controlling cell proliferation and death, such as Tyrosine Kinase Receptors (RTKs) for growth factors, are among the best targets for this type of therapeutic approach. Two classes of compounds targeting RTKs are currently used in clinical practice: monoclonal antibodies and tyrosine kinase inhibitors. The era of targeted therapy began with the approval of Trastuzumab, a monoclonal antibody against HER2, for treatment of metastatic breast cancer, and Imatinib, a small tyrosine kinase inhibitor targeting BCR-Abl, in Chronic Myeloid Leukemia. Despite the initial enthusiasm for the efficacy of these treatments, clinicians had to face soon the problem of relapse, as almost invariably cancer patients developed drug resistance, often due to the activation of alternative RTKs pathways. In this view, the rationale at the basis of targeting drugs is radically shifting. In the past, the main effort was aimed at developing highly specific inhibitors acting on single RTKs. Now, there is a general agreement that molecules interfering simultaneously with multiple RTKs might be more effective than single target agents. With the recent approval by FDA of Sorafenib and Sunitinib - targeting VEGFR, PDGFR, FLT-3 and c-Kit - a different scenario has been emerging, where a new generation of anti-cancer drugs, able to inhibit more than one pathway, would probably play a major role.
Export Options
About this article
Cite this article as:
Giordano S. and Petrelli A., From Single- to Multi-Target Drugs in Cancer Therapy: When Aspecificity Becomes an Advantage, Current Medicinal Chemistry 2008; 15 (5) . https://dx.doi.org/10.2174/092986708783503212
DOI https://dx.doi.org/10.2174/092986708783503212 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Synthesis and Biological Evaluation of New Naphthoquinones Derivatives
Current Organic Synthesis Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry The Role of Iron Chelation in Cancer Therapy
Current Medicinal Chemistry Cellular Senescence and Anti-Cancer Therapy
Current Drug Targets Different Concepts of Drug Delivery in Disease Entities
Mini-Reviews in Medicinal Chemistry Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases
Current Pharmaceutical Design Neurological Involvement in Rheumatoid Arthritis
Current Immunology Reviews (Discontinued) Anti-TNF-α Antibody Therapies in Autoimmune Diseases
Current Topics in Medicinal Chemistry Cannabis-Derived Substances in Cancer Therapy – An Emerging Anti- Inflammatory Role for the Cannabinoids
Current Clinical Pharmacology Role of Unani Medicines in Cancer Control and Management
Current Drug Therapy Lectin Microarrays: A Powerful Tool for Glycan-Based Biomarker Discovery
Combinatorial Chemistry & High Throughput Screening Targeting Epigenetics through Histone Deacetylase Inhibitors in Acute Lymphoblastic Leukemia
Current Cancer Drug Targets Targeting Angiogenesis for Treatment of NSCLC Brain Metastases
Current Cancer Drug Targets Drug Metabolism and Pharmacokinetic Diversity of Ranunculaceae Medicinal Compounds
Current Drug Metabolism NBS1 Heterozygosity and Cancer Risk
Current Genomics Understanding Epithelial-Mesenchymal Transition may Reveal Novel Therapeutic Targets for Oral Squamous Cell Carcinoma
Current Cancer Therapy Reviews Aflibercept (VEGF-TRAP): The Next Anti-VEGF Drug
Inflammation & Allergy - Drug Targets (Discontinued) Recent Advances in the Synthesis of 1-Monosubstituted 1,2,3-Triazoles
Mini-Reviews in Medicinal Chemistry From Physiome to Pathome: A Systems Biology Model of Major Depressive Disorder and the Psycho-Immune-Neuroendocrine Network
Current Psychiatry Reviews Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review
Current Drug Targets