Abstract
Malignant melanoma is the most aggressive and life-threatening skin cancer. Melanoma develops in melanocytes and is characterized by a very high tendency to spread to other parts of the body. Its pathogenesis depends on DNA mutations leading to the activation of oncogenes or to the inactivation of suppressor genes. The identification of misregulations in intracellular signal transduction pathways has provided an opportunity for the development of mutation-specific inhibitors, which specifically target the mutated signaling cascades. Over the last few years, clinical trials with MAPK pathway inhibitors have shown significant clinical activity in melanoma; however, their efficacy is limited due to the onset of acquired resistance. This has prompted a large set of preclinical studies looking at new approaches of pathway- or target-specific inhibitors. This review gives an overview of the latest developments of small molecule targeting multiple molecular pathways in both preclinical and clinical melanoma settings, with particular emphasis on additional strategies to tackle the reduced responsiveness to inhibitor treatment as possible future directions.
Keywords: Melanoma, metastasis, small molecules, targeted therapies, drug-resistance, MAPK pathway, cell cycle control.
Current Medicinal Chemistry
Title:Small Molecule Drugs and Targeted Therapy for Melanoma: Current Strategies and Future Directions
Volume: 24 Issue: 21
Author(s): Carmen Cerchia and Antonio Lavecchia*
Affiliation:
- Department of Pharmacy, “Drug Discovery” Laboratory, University of Napoli “Federico II”, via D. Montesano 49, I-80131 Napoli,Italy
Keywords: Melanoma, metastasis, small molecules, targeted therapies, drug-resistance, MAPK pathway, cell cycle control.
Abstract: Malignant melanoma is the most aggressive and life-threatening skin cancer. Melanoma develops in melanocytes and is characterized by a very high tendency to spread to other parts of the body. Its pathogenesis depends on DNA mutations leading to the activation of oncogenes or to the inactivation of suppressor genes. The identification of misregulations in intracellular signal transduction pathways has provided an opportunity for the development of mutation-specific inhibitors, which specifically target the mutated signaling cascades. Over the last few years, clinical trials with MAPK pathway inhibitors have shown significant clinical activity in melanoma; however, their efficacy is limited due to the onset of acquired resistance. This has prompted a large set of preclinical studies looking at new approaches of pathway- or target-specific inhibitors. This review gives an overview of the latest developments of small molecule targeting multiple molecular pathways in both preclinical and clinical melanoma settings, with particular emphasis on additional strategies to tackle the reduced responsiveness to inhibitor treatment as possible future directions.
Export Options
About this article
Cite this article as:
Cerchia Carmen and Lavecchia Antonio*, Small Molecule Drugs and Targeted Therapy for Melanoma: Current Strategies and Future Directions, Current Medicinal Chemistry 2017; 24 (21) . https://dx.doi.org/10.2174/0929867324666170414163937
DOI https://dx.doi.org/10.2174/0929867324666170414163937 |
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
-
Conventional Anticancer Therapeutics and Telomere Maintenance Mechanisms
Current Pharmaceutical Design Geldanamycin, Radicicol, and Chimeric Inhibitors of the Hsp90 Nterminal ATP Binding Site
Current Topics in Medicinal Chemistry Nanostructures for Drug Delivery to the Brain
Current Medicinal Chemistry Adhesion Molecules in Lung Cancer: Implications in the Pathogenesis and Management
Current Pharmaceutical Design Mechanisms of Action of Anesthetics for the Modulation of Perioperative Thrombosis: Evidence for Immune Mechanisms from Basic and Clinical Studies
Current Pharmaceutical Design Innate Immune System Modulation During Aging: Contributions of Macrophages and Dendritic Cells
Current Immunology Reviews (Discontinued) Repurposing of Benzimidazole Scaffolds for HER2 Positive Breast Cancer Therapy: An <i>In-Silico</i> Approach
Current Drug Research Reviews The Extracellular Matrix Regulates Cancer Progression and Therapy Response: Implications for Prognosis and Treatment
Current Pharmaceutical Design The cytotoxic effect of GW843682X on nasopharyngeal carcinoma
Anti-Cancer Agents in Medicinal Chemistry Gambogic Acid is a Novel Anti-cancer Agent that Inhibits Cell Proliferation, Angiogenesis and Metastasis
Anti-Cancer Agents in Medicinal Chemistry Mycotherapy of Cancer: An Update on Cytotoxic and Antitumor Activities of Mushrooms, Bioactive Principles and Molecular Mechanisms of their Action
Current Topics in Medicinal Chemistry Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase
Recent Patents on Anti-Cancer Drug Discovery Mevalonate Kinase Deficiency: Disclosing the Role of Mevalonate Pathway Modulation in Inflammation
Current Pharmaceutical Design Protease Inhibitors in the Clinic
Medicinal Chemistry Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Current Pharmaceutical Design Antiangiogenic Resistance and Cancer Metabolism: Opportunities for Synthetic Lethality
Current Drug Targets Exosomes Harnessed as Nanocarriers for Cancer Therapy - Current Status and Potential for Future Clinical Applications
Current Molecular Medicine Polymers Based on Phenyl Boric Acid in Tumor-Targeted Therapy
Anti-Cancer Agents in Medicinal Chemistry WT1 Peptide Vaccine as a Paradigm for “Cancer Antigen-Derived Peptide”-Based Immunotherapy for Malignancies: Successful Induction of Anti-Cancer Effect by Vaccination with a Single Kind of WT1 Peptide
Anti-Cancer Agents in Medicinal Chemistry Surgical Options for Management of Malignant Pleural Mesothelioma in the Current Era
Current Respiratory Medicine Reviews