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 |
- 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
-
Endothelial Function Assessment in Complicated Hypertension
Current Pharmaceutical Design Dexrazoxane for the Prevention of Cardiac Toxicity and Treatment of Extravasation Injury from the Anthracycline Antibiotics
Current Pharmaceutical Biotechnology Recent Developments on Endothelin Antagonists as Immunomodulatory Drugs - from Infection to Transplantation Medicine
Recent Patents on Cardiovascular Drug Discovery Preclinical Evaluation of a Zinc Finger Inhibitor Targeting Lentivirus Nucleocapsid Protein in SIV-Infected Monkeys
Current HIV Research β-Adrenergic Receptor Gene Polymorphisms and its Relationship with Heart Failure
Current Vascular Pharmacology Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?
Current Pharmacogenomics and Personalized Medicine The Detrimental Effect of Smoking on Female Fertility and IVF Success
Current Women`s Health Reviews Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential
Current Medicinal Chemistry Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis
Current Vascular Pharmacology Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders
Current Drug Metabolism The Prevalence and Progression of Arterial Calcification in Patients with End-Stage Renal Disease
Vascular Disease Prevention (Discontinued) The Cardiovascular Protective Effects of Chrysin: A Narrative Review on Experimental Researches
Cardiovascular & Hematological Agents in Medicinal Chemistry Cytotoxic Properties of Clofibrate and other Peroxisome Proliferators: Relevance to Cancer Progression
Current Medicinal Chemistry Antithrombotic Therapy for Transcatheter Valvular Interventions: A Revisit
Current Vascular Pharmacology The Minority Aging Research Study: Ongoing Efforts to Obtain Brain Donation in African Americans without Dementia
Current Alzheimer Research A Review of Statistical and Machine Learning Techniques for Microvascular Complications in Type 2 Diabetes
Current Diabetes Reviews Superoxide Anion Radical: Generation and Detection in Cellular and Non-Cellular Systems
Current Medicinal Chemistry Effects of Acarbose on Proinsulin and Insulin Secretion and their Potential Significance for the Intermediary Metabolism and Cardiovascular System
Current Diabetes Reviews The Concomitance of Hypertension and Diabetes Exacerbating Retinopathy: The Role of Inflammation and Oxidative Stress.
Current Clinical Pharmacology 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