Abstract
Melanoma, a malignant tumor of melanocytes, causes the majority (75%) of all skin cancer-related deaths. The overall efficacy of different anti-cancer therapies on metastatic melanoma is quite limited, due to its high resistance to all forms of conventional treatments, including chemotherapy, radiotherapy and immunotherapy, leading to low patient survival rates.
The present review identifies possible strategies for the treatment of advanced melanoma and describes two novel agents, Ipilimumab and Vemurafenib, which may now be useful for clinical practice.
Ipilimumab, a humanized, IgG1 monoclonal antibody, acts through immune-modulation since it blocks cytotoxic Tlymphocyte- associated antigen-4 (CTLA-4), producing favourable antitumor immune system responses and reducing tolerance to tumor-associated antigens. Vemurafenib is a novel oral small-molecule kinase inhibitor with high selectivity and efficacy toward a specific mutated oncogenic BRAF-signalling mediator. The mechanism of action of Vemurafenib involves selective inhibition of the mutated BRAFV600E kinase that leads to reduced signalling through the aberrant MAPK pathway. However, as patients commonly develop Vemurafenib resistance, clinical trials of Vemurafenib in combination with Ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide more effective regimens with longterm clinical benefits, emphasizing the importance of simultaneously targeting several pathways.
As both drugs had only modest effects on median survival, new therapeutic combinations are needed, such as BRAF inhibitors with MEK inhibitors or combinations of immunomodulators and pathway inhibitors. Such strategies should have the potential of maximizing antitumor effect while minimizing and improving clinical benefit. Nevertheless, these two new agents open a promising view into an effective management of melanoma.
Keywords: BRAFV600E mutation, Clinical investigation, Immunotherapy, Ipilimumab, Melanoma, Vemurafenib.
Current Cancer Drug Targets
Title:Ipilimumab and Vemurafenib: Two Different Routes for Targeting Melanoma
Volume: 13 Issue: 8
Author(s): Ana Burgeiro, Faustino Mollinedo and Paulo J. Oliveira
Affiliation:
Keywords: BRAFV600E mutation, Clinical investigation, Immunotherapy, Ipilimumab, Melanoma, Vemurafenib.
Abstract: Melanoma, a malignant tumor of melanocytes, causes the majority (75%) of all skin cancer-related deaths. The overall efficacy of different anti-cancer therapies on metastatic melanoma is quite limited, due to its high resistance to all forms of conventional treatments, including chemotherapy, radiotherapy and immunotherapy, leading to low patient survival rates.
The present review identifies possible strategies for the treatment of advanced melanoma and describes two novel agents, Ipilimumab and Vemurafenib, which may now be useful for clinical practice.
Ipilimumab, a humanized, IgG1 monoclonal antibody, acts through immune-modulation since it blocks cytotoxic Tlymphocyte- associated antigen-4 (CTLA-4), producing favourable antitumor immune system responses and reducing tolerance to tumor-associated antigens. Vemurafenib is a novel oral small-molecule kinase inhibitor with high selectivity and efficacy toward a specific mutated oncogenic BRAF-signalling mediator. The mechanism of action of Vemurafenib involves selective inhibition of the mutated BRAFV600E kinase that leads to reduced signalling through the aberrant MAPK pathway. However, as patients commonly develop Vemurafenib resistance, clinical trials of Vemurafenib in combination with Ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide more effective regimens with longterm clinical benefits, emphasizing the importance of simultaneously targeting several pathways.
As both drugs had only modest effects on median survival, new therapeutic combinations are needed, such as BRAF inhibitors with MEK inhibitors or combinations of immunomodulators and pathway inhibitors. Such strategies should have the potential of maximizing antitumor effect while minimizing and improving clinical benefit. Nevertheless, these two new agents open a promising view into an effective management of melanoma.
Export Options
About this article
Cite this article as:
Burgeiro Ana, Mollinedo Faustino and Oliveira J. Paulo, Ipilimumab and Vemurafenib: Two Different Routes for Targeting Melanoma, Current Cancer Drug Targets 2013; 13 (8) . https://dx.doi.org/10.2174/15680096113139990080
DOI https://dx.doi.org/10.2174/15680096113139990080 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Application of Bacterial Nanocellulose in Cancer Drug Delivery: A Review
Current Pharmaceutical Design The Use of Transient Expression Systems for the Rapid Production of Virus-like Particles in Plants
Current Pharmaceutical Design Application of Nanotechnology in the Treatment and Diagnosis of Gastrointestinal Cancers: Review of Recent Patents
Recent Patents on Anti-Cancer Drug Discovery Oxaliplatin-mediated Inhibition of Survivin Increases Sensitivity of Head and Neck Squamous Cell Carcinoma Cell Lines to Paclitaxel
Current Cancer Drug Targets Axitinib in the Treatment of Head and Neck Malignancies
Current Clinical Pharmacology Prodrugs in Photodynamic Anticancer Therapy
Current Pharmaceutical Design Antigenic Differences Between Normal and Malignant Cells as a Basis for Treatment of Intracerebral Neoplasms Using a DNA-Based Vaccine
Current Genomics Cancer Kinases and its Novel Inhibitors: Past, Present and Future Challenges
Current Drug Targets The Crosstalk of RAS with the TGF-β Family During Carcinoma Progression and its Implications for Targeted Cancer Therapy
Current Cancer Drug Targets Insight View on Possible Role of Fluoroquinolones in Cancer Therapy
Current Topics in Medicinal Chemistry Epigenetic Regulators Governing Cancer Stem Cells and Epithelial- Mesenchymal Transition in Oral Squamous Cell Carcinoma
Current Stem Cell Research & Therapy KiSS1-Induced GPR54 Signaling Inhibits Breast Cancer Cell Migration and Epithelial-Mesenchymal Transition via Protein Kinase D1
Current Molecular Medicine Melanoma Detection and Classification using Computerized Analysis of Dermoscopic Systems: A Review
Current Medical Imaging C-11 Radiochemistry in Cancer Imaging Applications
Current Topics in Medicinal Chemistry Methylation of ZNF331 Promotes Cell Invasion and Migration in Human Esophageal Cancer
Current Protein & Peptide Science NF-κB Inhibitors in Head and Neck Cancer
Letters in Drug Design & Discovery All for Statins and Statins for All; An Update
Current Pharmaceutical Design Oral Precancerous Lesions Show Increased Levels of Glutathione Compared to Cancerous Tissue
Current Nutrition & Food Science Novel Systemic Drugs for Cutaneous T-Cell Lymphoma
Recent Patents on Anti-Cancer Drug Discovery Patents in Cancer Stem Cells
Recent Patents on Biomarkers