Abstract
One of the major causes of failure in cancer chemotherapy is multidrug resistance (MDR), where cancer cells simultaneously become resistant to different anticancer drugs. Over-expression of membrane efflux pumps like Pglycoprotein (P-gp) that recognizes different chemotherapeutic agents and transports them out of the cell, plays a major role in MDR. The shortcoming of P-gp inhibitors in clinic has been attributed to their non-specific action on P-gp and/or non-selective distribution to non-target organs that leads to intolerable side effects by the P-gp inhibitor at doses required for P-gp inhibition upon systemic administration. Another major issue is the reduced elimination of P-gp substrates (e.g. anticancer drugs) and intolerable toxicities by anticancer drugs when co-administered with P-gp inhibitors. To overcome these shortcomings, new generation of P-gp inhibitors with improved specificity for P-gp have been developed. More recently, attention has been paid to the use of drug delivery systems primarily to restrict P-gp inhibition to tumor and reduce the non-selective inhibition of P-gp in non-target organs. This review will provide an overview and update on the status of P-gp inhibition approaches and the role of drug delivery systems in overcoming P-gp mediated MDR.
Keywords: Cancer, chemotherapy, drug delivery systems, gene silencing, multidrug resistance, P-glycoprotein, P-glycoprotein inhibitors
Current Cancer Drug Targets
Title:P-glycoprotein Inhibition as a Therapeutic Approach for Overcoming Multidrug Resistance in Cancer: Current Status and Future Perspectives
Volume: 13 Issue: 3
Author(s): Ziyad Binkhathlan and Afsaneh Lavasanifar
Affiliation:
Keywords: Cancer, chemotherapy, drug delivery systems, gene silencing, multidrug resistance, P-glycoprotein, P-glycoprotein inhibitors
Abstract: One of the major causes of failure in cancer chemotherapy is multidrug resistance (MDR), where cancer cells simultaneously become resistant to different anticancer drugs. Over-expression of membrane efflux pumps like Pglycoprotein (P-gp) that recognizes different chemotherapeutic agents and transports them out of the cell, plays a major role in MDR. The shortcoming of P-gp inhibitors in clinic has been attributed to their non-specific action on P-gp and/or non-selective distribution to non-target organs that leads to intolerable side effects by the P-gp inhibitor at doses required for P-gp inhibition upon systemic administration. Another major issue is the reduced elimination of P-gp substrates (e.g. anticancer drugs) and intolerable toxicities by anticancer drugs when co-administered with P-gp inhibitors. To overcome these shortcomings, new generation of P-gp inhibitors with improved specificity for P-gp have been developed. More recently, attention has been paid to the use of drug delivery systems primarily to restrict P-gp inhibition to tumor and reduce the non-selective inhibition of P-gp in non-target organs. This review will provide an overview and update on the status of P-gp inhibition approaches and the role of drug delivery systems in overcoming P-gp mediated MDR.
Export Options
About this article
Cite this article as:
Binkhathlan Ziyad and Lavasanifar Afsaneh, P-glycoprotein Inhibition as a Therapeutic Approach for Overcoming Multidrug Resistance in Cancer: Current Status and Future Perspectives, Current Cancer Drug Targets 2013; 13 (3) . https://dx.doi.org/10.2174/15680096113139990076
DOI https://dx.doi.org/10.2174/15680096113139990076 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature
Current Cardiology Reviews Approaches to Target Profiling of Natural Products
Current Medicinal Chemistry New and Highly Potent Antitumor Natural Products from Marine-Derived Fungi: Covering the Period from 2003 to 2012
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Drug Targets in Viral Infections (Guest Editor: Jean-Marc Sabatier)]
Infectious Disorders - Drug Targets Protective Effects of Curcumin against Iron-induced Toxicity
Current Pharmaceutical Biotechnology The Role of YY1 in Oncogenesis and Its Potential as a Drug Target in Cancer Therapies
Current Cancer Drug Targets Aryltetralin-type Lignan of Podophyllum: A Comprehensive Review
The Natural Products Journal Targeting Epidermal Growth Factor Receptor in Solid Tumors: Critical Evaluation of the Biological Importance of Therapeutic Monoclonal Antibodies
Current Medicinal Chemistry Biotransformations of Prenylated Hop Flavonoids for Drug Discovery and Production
Current Drug Metabolism HPV Screening: Available Data and Recommendations for Clinical Practice
Current Cancer Therapy Reviews Genetic Markers of Osteoarthritis
Current Rheumatology Reviews Cell Arrest and Apoptosis Induced by the Next Generation of Vanadium Based Drugs: Action Mechanism to Structure Relation and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Type Specific Human Papilloma Virus Prevalence and Distribution in Women with Abnormal Cervical Cytology: A Single Centre Retrospective Observational Study in the Emirate of Abu Dhabi
New Emirates Medical Journal Antibody Immobilization Techniques in Mass Sensitive Immunosensor: Enhanced Sensitivity through Limited Mass Load
Current Analytical Chemistry Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry miRNA and Proteomic Dysregulation in Non-Small Cell Lung Cancer in Response to Cigarette Smoke
MicroRNA Novel Mast Cell-Stabilising Amine Derivatives of 3,4-Dihydronaphthalen-1(2H)-one and 6,7,8,9-Tetrahydro-5H-benzo[7]annulen-5-one
Medicinal Chemistry Vitamin D Receptor is a Novel Drug Target for Ovarian Cancer Treatment
Current Cancer Drug Targets Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy
Current Drug Targets