Abstract
Mesothelin, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, is a potential target for antibody-based cancer therapy due to its high expression in mesothelioma, ovarian cancer, pancreatic cancer, cholangiocarcinoma and other cancers. The SS1P immunotoxin and MORAb-009 (amatuximab), a chimeric monoclonal antibody, are currently being evaluated in clinical trials. In this review, we discuss the role of mesothelin in cancer progression and provide new insights into mesothelin-targeted cancer therapy. Recent studies highlight three mechanisms by which mesothelin plays a role in cancer progression. First, mesothelin may aid in the peritoneal implantation and metastasis of tumors through its interaction with mucin MUC16 (also known as CA125). Second, mesothelin may promote cancer cell survival and proliferation via the NF-κB signaling pathway. Finally, mesothelin expression promotes resistance to certain chemotherapy drugs such as TNF-α, paclitaxel, and a combination of platinum and cyclophosphamide. However, its cancerspecific expression makes mesothelin a potential target for monoclonal antibody therapy. New human monoclonal antibodies targeting mesothelin have been isolated by phage display technology and may provide opportunities for novel cancer therapy.
Keywords: Antibody dependent cell mediated cytotoxicity/ADCC, Apoptosis, Cell surface proteins, Cell survival/proliferation, Complement dependent cytotoxicity/CDC, Human monoclonal antibodies, Immunotoxin, Mesothelin, MORAb-009/amatuximab, MUC16/CA125, NF-κB, PI3K/Akt, SS1P
Anti-Cancer Agents in Medicinal Chemistry
Title:The Role of Mesothelin in Tumor Progression and Targeted Therapy
Volume: 13 Issue: 2
Author(s): Zhewei Tang, Min Qian and Mitchell Ho
Affiliation:
Keywords: Antibody dependent cell mediated cytotoxicity/ADCC, Apoptosis, Cell surface proteins, Cell survival/proliferation, Complement dependent cytotoxicity/CDC, Human monoclonal antibodies, Immunotoxin, Mesothelin, MORAb-009/amatuximab, MUC16/CA125, NF-κB, PI3K/Akt, SS1P
Abstract: Mesothelin, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, is a potential target for antibody-based cancer therapy due to its high expression in mesothelioma, ovarian cancer, pancreatic cancer, cholangiocarcinoma and other cancers. The SS1P immunotoxin and MORAb-009 (amatuximab), a chimeric monoclonal antibody, are currently being evaluated in clinical trials. In this review, we discuss the role of mesothelin in cancer progression and provide new insights into mesothelin-targeted cancer therapy. Recent studies highlight three mechanisms by which mesothelin plays a role in cancer progression. First, mesothelin may aid in the peritoneal implantation and metastasis of tumors through its interaction with mucin MUC16 (also known as CA125). Second, mesothelin may promote cancer cell survival and proliferation via the NF-κB signaling pathway. Finally, mesothelin expression promotes resistance to certain chemotherapy drugs such as TNF-α, paclitaxel, and a combination of platinum and cyclophosphamide. However, its cancerspecific expression makes mesothelin a potential target for monoclonal antibody therapy. New human monoclonal antibodies targeting mesothelin have been isolated by phage display technology and may provide opportunities for novel cancer therapy.
Export Options
About this article
Cite this article as:
Tang Zhewei, Qian Min and Ho Mitchell, The Role of Mesothelin in Tumor Progression and Targeted Therapy, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (2) . https://dx.doi.org/10.2174/1871520611313020014
DOI https://dx.doi.org/10.2174/1871520611313020014 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Natural Products Targeting Autophagy via the PI3K/Akt/mTOR Pathway as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Phosphoinositide-3-kinases as the Novel Therapeutic Targets for the Inflammatory Diseases: Current and Future Perspectives
Current Drug Targets Applications of Nanocarbons in Bio-Medical Devices
Recent Innovations in Chemical Engineering Applications of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) in Pulmonary Disease
Current Respiratory Medicine Reviews Combined Anticancer Therapies: An Overview of the Latest Applications
Anti-Cancer Agents in Medicinal Chemistry Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer
Current Pharmaceutical Design Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Anticancer Drug Discovery Targeting DNA Hypermethylation
Current Medicinal Chemistry Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Antibody Engineering for Targeted Therapy of Cancer Recombinant Fv-Immunotoxins
Current Pharmaceutical Biotechnology Onconase and Amphinase, the Antitumor Ribonucleases from Rana pipiens Oocytes
Current Pharmaceutical Biotechnology Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects
Current Cancer Drug Targets Reversing Aberrant Methylation Patterns in Cancer
Current Medicinal Chemistry Airway Fibroblast Secretory Products Enhance Cell Migration
Current Proteomics Regulation of MET Receptor Signaling by SOCS1 and its Implications for Hepatocellular Carcinoma
Current Pharmaceutical Design Combination of Photodynamic Therapy with Anti-Cancer Agents
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Proteomics Gefitinib Targets EGFR Dimerization and ERK1/2 Phosphorylation to Inhibit Pleural Mesothelioma Cell Proliferation
Current Cancer Drug Targets Lipid-Based Vectors for Therapeutic mRNA-Based Anti-Cancer Vaccines
Current Pharmaceutical Design