Abstract
Malignant mesothelioma is a highly invasive tumor originating from the mesothelial linings of the pleura, peritoneum and pericardium. It is seldom amenable to surgical intervention and poorly responsive to radiotherapy, leaving chemotherapy as the main therapeutic option for most patients. The development of effective drug regimens against mesothelioma has proven extremely difficult and a standard first-line treatment for patients with unresectable tumors has not been established until recently. Despite the benefits obtained with this newly validated standard of care, which is based on the combination of pemetrexed and cisplatin, the prognosis for mesothelioma patients remains poor, median survival is still less than two years and more active treatments are urgently needed. This article will focus on the molecular basis providing the rationale for targeted interventions against mesothelioma and will review targeted agents under evaluation as new potential therapeutic options for mesothelioma patients. Such agents include inhibitors of growth factor receptors, ligands and intracellular effectors. The agents targeting vascular endothelial growth factor signaling are of particular interest, due to the involvement of this pathway both in tumor angiogenesis and autocrine stimulation of mesothelioma cell growth. Alternative approaches are based on inhibitors of the ubiquitin-proteasome pathway and of histone deacetylases which, notwithstanding the functional divergence of the corresponding targets, share the ability to determine a wide modulation of the cancer cell phenotype that can lead to cell cycle arrest, apoptosis and sensitization to different antineoplastic treatments. A recombinant immunotoxin targeted to the membrane antigen mesothelin is an additional agent whose activity is being evaluated in mesothelioma patients.
Keywords: Mesothelioma, molecular therapy, receptor tyrosine kinase inhibitors, bevacizumab, rapamycin, bortezomib, histone deacetylase inhibitors, mesothelin
Current Medicinal Chemistry
Title: Molecular Targets and Targeted Therapies for Malignant Mesothelioma
Volume: 15 Issue: 9
Author(s): Camilla Palumbo, Roberto Bei, Antonio Procopio and Andrea Modesti
Affiliation:
Keywords: Mesothelioma, molecular therapy, receptor tyrosine kinase inhibitors, bevacizumab, rapamycin, bortezomib, histone deacetylase inhibitors, mesothelin
Abstract: Malignant mesothelioma is a highly invasive tumor originating from the mesothelial linings of the pleura, peritoneum and pericardium. It is seldom amenable to surgical intervention and poorly responsive to radiotherapy, leaving chemotherapy as the main therapeutic option for most patients. The development of effective drug regimens against mesothelioma has proven extremely difficult and a standard first-line treatment for patients with unresectable tumors has not been established until recently. Despite the benefits obtained with this newly validated standard of care, which is based on the combination of pemetrexed and cisplatin, the prognosis for mesothelioma patients remains poor, median survival is still less than two years and more active treatments are urgently needed. This article will focus on the molecular basis providing the rationale for targeted interventions against mesothelioma and will review targeted agents under evaluation as new potential therapeutic options for mesothelioma patients. Such agents include inhibitors of growth factor receptors, ligands and intracellular effectors. The agents targeting vascular endothelial growth factor signaling are of particular interest, due to the involvement of this pathway both in tumor angiogenesis and autocrine stimulation of mesothelioma cell growth. Alternative approaches are based on inhibitors of the ubiquitin-proteasome pathway and of histone deacetylases which, notwithstanding the functional divergence of the corresponding targets, share the ability to determine a wide modulation of the cancer cell phenotype that can lead to cell cycle arrest, apoptosis and sensitization to different antineoplastic treatments. A recombinant immunotoxin targeted to the membrane antigen mesothelin is an additional agent whose activity is being evaluated in mesothelioma patients.
Export Options
About this article
Cite this article as:
Palumbo Camilla, Bei Roberto, Procopio Antonio and Modesti Andrea, Molecular Targets and Targeted Therapies for Malignant Mesothelioma, Current Medicinal Chemistry 2008; 15 (9) . https://dx.doi.org/10.2174/092986708783955446
DOI https://dx.doi.org/10.2174/092986708783955446 |
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
-
Harnessing Phage Display for the Discovery of Peptide-Based Drugs and Monoclonal Antibodies
Current Medicinal Chemistry Inhibitors of HDACs - Effective Drugs Against Cancer?
Current Cancer Drug Targets Pemetrexed: Potential Role in the Adjuvant Chemotherapy of Non-Small Cell Lung Cancer
Current Drug Targets Progress in the Preclinical Discovery and Clinical Development of Class I and Dual Class I/IV Phosphoinositide 3-Kinase (PI3K) Inhibitors
Current Medicinal Chemistry Cancer Stem Cells: The ‘Achilles Heel’ of Chemo-Resistant Tumors
Recent Patents on Anti-Cancer Drug Discovery Interplay between DNA Methyltransferase 1 and microRNAs During Tumorigenesis
Current Drug Targets Cationic Liposome Mediated Delivery of FUS1 and hIL-12 Coexpression Plasmid Demonstrates Enhanced Activity against Human Lung Cancer
Current Cancer Drug Targets Meet Our Editorial Board Member:
Current Respiratory Medicine Reviews Cytotoxic Effect of the Red Beetroot (Beta vulgaris L.) Extract Compared to Doxorubicin (Adriamycin) in the Human Prostate (PC-3) and Breast (MCF-7) Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery
Anti-Cancer Agents in Medicinal Chemistry Role of NF-κB and NF-κB-regulated Gene Products in Chemoresistance and Radioresistance
Current Cancer Therapy Reviews Platelet-Rich Plasma Induces Mixed Osteogenic/Osteoclastogenic Phenotype in Osteosarcoma SaOS-2 Cells: Role of TGF-Beta
Current Pharmaceutical Biotechnology Metallothioneins and Cancer
Current Protein & Peptide Science Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics
Current Medicinal Chemistry Redox-inactive Analogue of Tocotrienol as a Potential Anti-cancer Agent
Anti-Cancer Agents in Medicinal Chemistry Vascular Injury During Elevated Glucose can be Mitigated by Erythropoietin and Wnt Signaling
Current Neurovascular Research 3-Bromopyruvic Acid, A Hexokinase II Inhibitor, is an Effective Antitumor Agent on the Hepatoma Cells : in vitro and in vivo Findings
Anti-Cancer Agents in Medicinal Chemistry Overview of the Formulations and Analogs in the Taxanes' Story
Current Medicinal Chemistry Chemical Genomics and Emerging DNA Technologies in the Identification of Drug Mechanisms and Drug Targets
Current Topics in Medicinal Chemistry