Abstract
A range of experimental and clinical data suggests strongly (i) that metastatic progression in carcinomas is accompanied (maybe even preceded) by upregulation of functional voltage-gated sodium channels (VGSCs) and (ii) that VGSC activity enhances cancer cell invasiveness. First, this review outlines the available in vitro and in vivo evidence for the VGSC expression and its proposed pathophysiological role. Second, we question the mechanism(s) whereby VGSC activity can induce such a cancer-promoting effect. We advance the hypothesis that it is the hypoxia-sensitive persistent component of the VGSC current (INaP) that is central to the phenomenon. Indeed, blockers of INaP are very effective in suppressing cancer cell invasiveness in vitro. Based upon these data, UK and international patent applications have been filed which describe the use of INaP blockers, like ranolazine (“Ranexa”) and riluzole (“Rilutex”), as anti-metastatic agents. Importantly, since these drugs are already in clinical use, against conditions like cardiac angina and amyotrophic lateral scelerosis, there are no issues of dosage, unacceptable side effects or long-term use. Thus, INaP blockers have the potential to turn cancer into a chronic condition.
Keywords: Hypoxia, metastasis, persistent current, ranolazine, riluzole, voltage-gated sodium channel
Recent Patents on Anti-Cancer Drug Discovery
Title:Persistent Current Blockers of Voltage-Gated Sodium Channels: A Clinical Opportunity for Controlling Metastatic Disease
Volume: 8 Issue: 1
Author(s): Mustafa B.A. Djamgoz and Rustem Onkal
Affiliation:
Keywords: Hypoxia, metastasis, persistent current, ranolazine, riluzole, voltage-gated sodium channel
Abstract: A range of experimental and clinical data suggests strongly (i) that metastatic progression in carcinomas is accompanied (maybe even preceded) by upregulation of functional voltage-gated sodium channels (VGSCs) and (ii) that VGSC activity enhances cancer cell invasiveness. First, this review outlines the available in vitro and in vivo evidence for the VGSC expression and its proposed pathophysiological role. Second, we question the mechanism(s) whereby VGSC activity can induce such a cancer-promoting effect. We advance the hypothesis that it is the hypoxia-sensitive persistent component of the VGSC current (INaP) that is central to the phenomenon. Indeed, blockers of INaP are very effective in suppressing cancer cell invasiveness in vitro. Based upon these data, UK and international patent applications have been filed which describe the use of INaP blockers, like ranolazine (“Ranexa”) and riluzole (“Rilutex”), as anti-metastatic agents. Importantly, since these drugs are already in clinical use, against conditions like cardiac angina and amyotrophic lateral scelerosis, there are no issues of dosage, unacceptable side effects or long-term use. Thus, INaP blockers have the potential to turn cancer into a chronic condition.
Export Options
About this article
Cite this article as:
B.A. Djamgoz Mustafa and Onkal Rustem, Persistent Current Blockers of Voltage-Gated Sodium Channels: A Clinical Opportunity for Controlling Metastatic Disease, Recent Patents on Anti-Cancer Drug Discovery 2013; 8 (1) . https://dx.doi.org/10.2174/1574892811308010066
DOI https://dx.doi.org/10.2174/1574892811308010066 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
Call for Papers in Thematic Issues
Novel anti-cancer drugs in photoimmunotherapy management: from bench to translational research
In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...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
-
Multiplex Analysis of Cardiac Hypertrophic Signaling: Reduced in vivo Phosphorylation of Glycogen Synthase Kinase-3β and Proline-Rich Akt Substrate (PRAS40)
Current Signal Transduction Therapy The Chemopreventive and Chemotherapeutic Potentials of Tea Polyphenols
Current Pharmaceutical Biotechnology Endocrine Therapies and QTc Prolongation
Current Drug Safety Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease
Current Medicinal Chemistry Protective Effect of Natural Antioxidants on Heart Against Ischemia-Reperfusion Damage
Current Pharmaceutical Biotechnology Sleep Apnea: an Underestimated Cause of Resistant Hypertension
Current Hypertension Reviews Prediction of Cardiovascular Risk Using Extreme Learning Machine-Tree Classifier on Apache Spark Cluster
Recent Advances in Computer Science and Communications Oncolytic Coxsackievirus and the Mechanisms of its Effects on Cancer: A Narrative Review
Current Cancer Therapy Reviews A Mini-Review on Cardiovascular and Hematological Complications of COVID-19
Coronaviruses Lipid-Lowering Drugs Acting at the Level of the Gastrointestinal Tract
Current Pharmaceutical Design Intracardiac Origin of Heart Rate Variability, Pacemaker Funny Current and their Possible Association with Critical Illness
Current Cardiology Reviews The Sour Taste-Modifying Protein (Miraculin), Tyrosinase Inhibitors and Antioxidants from Synsepalum dulcificum
Current Nutrition & Food Science Mechanisms of Neurodegeration in Type 2 Diabetes and the Neuroprotective Potential of Dipeptidyl Peptidase 4 Inhibitors
Current Medicinal Chemistry Psychological Stress and the Development of Heart Disease
Current Psychiatry Reviews Cardio-vascular Activity of Catestatin: Interlocking the Puzzle Pieces
Current Medicinal Chemistry PREFACE: “The Lower the Better” Association between White-coat Effect-excluded Blood Pressure and Cardiovascular Events in High-risk Hypertension: Insights from SPRINT
Current Hypertension Reviews CTLA-4Ig: Uses and Future Directions
Recent Patents on Inflammation & Allergy Drug Discovery Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients
Current Vascular Pharmacology Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?
Current Drug Targets Angiotensin Converting Enzyme Inhibitor in Coronary Artery Bypass Surgery
Drug Design Reviews - Online (Discontinued)