Abstract
Epithelial ovarian cancer is a major problem as about 75% of patients develop recurrence after initial primary treatment and tumors are often chemoresistant. This article reviews the role of the interleukin-6 (IL-6) in chemoresistance and suppression of tumor immunity in ovarian cancer and provides the rationale for modulating the IL-6/ IL-6 receptor (IL-6R) induced pathway as a potential new target for the treatment of ovarian cancer. IL-6 is elevated in serum and ascites of ovarian cancer patients and increased IL-6 levels correlate with chemoresistance and poor prognosis in these patients. IL-6 induced Jak/Stat3, Ras/MEK/ERK and PI3K/Ras signaling pathways lead to cell survival, proliferation, angiogenesis, and confers resistance to apoptosis induced by conventional therapies. Furthermore, IL-6 induces tumor-promoting macrophages which are known to foster tumor growth and suppress local immunity. However, direct proof of the clinical impact of IL-6 blocking on disease progression is missing necessiting further studies in which the IL-6(R) pathway is modulated and its clinical impact on (epithelial) ovarian cancer is tested.
Keywords: Ovarian cancer, interleukin-6, immunotherapy, Stat3, chemoresistance, tumor immunity, serum, ascites, cell survival, angiogenesis.
Current Pharmaceutical Design
Title:Interleukin-6/interleukin-6 Receptor Pathway as a New Therapy Target in Epithelial Ovarian Cancer
Volume: 18 Issue: 25
Author(s): Eveline M. Dijkgraaf, Marij J.P. Welters, Johan W.R. Nortier, Sjoerd H. van der Burg and Judith R. Kroep
Affiliation:
Keywords: Ovarian cancer, interleukin-6, immunotherapy, Stat3, chemoresistance, tumor immunity, serum, ascites, cell survival, angiogenesis.
Abstract: Epithelial ovarian cancer is a major problem as about 75% of patients develop recurrence after initial primary treatment and tumors are often chemoresistant. This article reviews the role of the interleukin-6 (IL-6) in chemoresistance and suppression of tumor immunity in ovarian cancer and provides the rationale for modulating the IL-6/ IL-6 receptor (IL-6R) induced pathway as a potential new target for the treatment of ovarian cancer. IL-6 is elevated in serum and ascites of ovarian cancer patients and increased IL-6 levels correlate with chemoresistance and poor prognosis in these patients. IL-6 induced Jak/Stat3, Ras/MEK/ERK and PI3K/Ras signaling pathways lead to cell survival, proliferation, angiogenesis, and confers resistance to apoptosis induced by conventional therapies. Furthermore, IL-6 induces tumor-promoting macrophages which are known to foster tumor growth and suppress local immunity. However, direct proof of the clinical impact of IL-6 blocking on disease progression is missing necessiting further studies in which the IL-6(R) pathway is modulated and its clinical impact on (epithelial) ovarian cancer is tested.
Export Options
About this article
Cite this article as:
M. Dijkgraaf Eveline, J.P. Welters Marij, W.R. Nortier Johan, H. van der Burg Sjoerd and R. Kroep Judith, Interleukin-6/interleukin-6 Receptor Pathway as a New Therapy Target in Epithelial Ovarian Cancer, Current Pharmaceutical Design 2012; 18 (25) . https://dx.doi.org/10.2174/138161212802002797
DOI https://dx.doi.org/10.2174/138161212802002797 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
A Prooxidant Mechanism for the Anticancer and Chemopreventive Properties of Plant Polyphenols
Current Drug Targets Pharmacogenetics of Drug Transporters and Its Impact on the Pharmacotherapy
Current Topics in Medicinal Chemistry Assessment and Management of the Adnexal Mass in the Pediatric Population
Current Women`s Health Reviews Multifaceted Role of Neuropilins in Cancer
Current Medicinal Chemistry Recent Advances, Issues and Patents on Medical Nanorobots
Recent Patents on Engineering Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine (Supplementry Material)
Current Cancer Drug Targets Doing the Puzzle of Steroid Hormone Action: Biological Functions, Physiological and Clinical Significance of Plasma Membrane-Residing Glucocorticoid Recognizing Proteins
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Metastasis-Associated Protein S100A4: Spotlight on its Role in Cell Migration
Current Cancer Drug Targets Roles of Natural Compounds from Medicinal Plants in Cancer Treatment: Structure and Mode of Action at Molecular Level
Medicinal Chemistry Comprehensive Review of Cancer Chemopreventive Agents Evaluated in Experimental Carcinogenesis Models and Clinical Trials
Current Medicinal Chemistry Aloperine Induces Apoptosis by a Reactive Oxygen Species Activation Mechanism in Human Ovarian Cancer Cells
Protein & Peptide Letters Nonviral Vectors for Cancer Gene Therapy: Prospects for Integrating Vectors and Combination Therapies
Current Gene Therapy The Role of NF-κB Inhibitors in Cell Response to Radiation
Current Medicinal Chemistry The Integrative Network of Gene Expression, MicroRNA, Methylation and Copy Number Variation in Colon and Rectal Cancer
Current Bioinformatics SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review
Current Topics in Medicinal Chemistry In vivo behavior and Safety of Lapatinib-Incorporated Lipid Nanoparticles
Current Pharmaceutical Biotechnology Pulmonary Drug Delivery System: A Novel Approach for Drug Delivery
Current Drug Therapy Apoptotic Potency of Angiostatic Compounds in the Treatment of Cancer
Current Pharmaceutical Biotechnology Insect Peptides – Perspectives in Human Diseases Treatment
Current Medicinal Chemistry Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology