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
-
Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry A Better Platinum-Based Anticancer Drug Yet to Come?
Anti-Cancer Agents in Medicinal Chemistry The Role of PET/CT and SPECT/CT in Oncology Drug Development
Current Molecular Imaging (Discontinued) From 2D to 3D - a New Dimension for Modelling the Effect of Natural Products on Human Tissue
Current Pharmaceutical Design Recent Advances in the Design and Synthesis of Small Molecule Carbonic Anhydrase IX Inhibitors
Current Topics in Medicinal Chemistry New Strategies in the Chemotherapy of Leukemia: Eradicating Cancer Stem Cells in Chronic Myeloid Leukemia
Current Cancer Drug Targets Pharmacological Therapy of Pericardial Diseases
Current Pharmaceutical Design Ewing Sarcoma Family Tumors: Past, Present and Future Prospects
Current Cancer Therapy Reviews Therapeutic Strategies for Targeting BRAF in Human Cancer
Reviews on Recent Clinical Trials Improvement of malignant pleural mesothelioma immunotherapy by epigenetic modulators
Current Topics in Medicinal Chemistry Angiogenesis and Angiogenic Inhibitors in Non Small Cell Lung Cancer
Current Angiogenesis (Discontinued) Current Status and Future Perspectives on Old Drug Repurposing for Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology Biology of Cox-2: An Application in Cancer Therapeutics
Current Drug Targets Adenoviral Vector-Mediated Gene Transfer for Human Gene Therapy
Current Gene Therapy α7-Nicotinic Acetylcholine Receptors: An Old Actor for New Different Roles
Current Drug Targets The Potential for Targeting Oncogenic WNT/β -Catenin Signaling in Therapy
Current Drug Targets Angiogenesis Inhibition: State of the Art, Forgotten Strategies and New Perspectives in Cancer Therapy
Current Cancer Therapy Reviews Inhibitors of HDACs - Effective Drugs Against Cancer?
Current Cancer Drug Targets HLA-G Expression in Cancers: Potential Role in Diagnosis, Prognosis and Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets