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
-
Sodium Selenite Decreased HDAC Activity, Cell Proliferation and Induced Apoptosis in Three Human Glioblastoma Cells
Anti-Cancer Agents in Medicinal Chemistry Pharmacological Approaches to Chronic Spinal Cord Injury
Current Pharmaceutical Design Spatio-Temporal Expression and Functional Analysis of miR-206 in Developing Orofacial Tissue
MicroRNA Obesity-Driven Inflammation and Colorectal Cancer
Current Medicinal Chemistry Recent Advances on Prediction of Human Papillomaviruses Risk Types
Current Drug Metabolism Anti Cancer Activity on Graviola, an Exciting Medicinal Plant Extract vs Various Cancer Cell Lines and a Detailed Computational Study on its Potent Anti-Cancerous Leads
Current Topics in Medicinal Chemistry Rediscovering Tocophersolan: A Renaissance for Nano-Based Drug Delivery and Nanotheranostic Applications
Current Drug Targets The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery
Current Pharmaceutical Design Precise Analysis of the Autofluorescence Characteristics of Rat Colon Under UVA and Violet Light Excitation
Current Pharmaceutical Biotechnology Comprehensive Analysis Reveals GPRIN1 is a Potential Biomarker for Non-sm all Cell Lung Cancer
Current Bioinformatics Identification of a Novel Intestinal First Pass Metabolic Pathway: NQO1 Mediated Quinone Reduction and Subsequent Glucuronidation
Current Drug Metabolism Advances of Infrared Spectroscopic Imaging and Mapping Technologies of Plant Material
Current Bioactive Compounds Identification and Characterization of the Binding Sites of P-Glycoprotein for Multidrug Resistance-Related Drugs and Modulators
Current Medicinal Chemistry - Anti-Cancer Agents Phytochemicals to Prevent Inflammation and Allergy
Recent Patents on Inflammation & Allergy Drug Discovery Hepatitis B Virus X Protein Modulates Chemokine CCL15 Upregulation in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs and Cancer Therapy – From Bystanders to Major Players
Current Medicinal Chemistry Targetting Esophageal and Gastric Cancers with Monoclonal Antibodies
Current Topics in Medicinal Chemistry Melatonin, A Natural Programmed Cell Death Inducer in Cancer
Current Medicinal Chemistry Animal Models of Carcinogenesis in Inflamed Colorectum: Potential Use in Chemoprevention Study
Current Drug Targets Treatment of GM2 Gangliosidosis in Adult Sandhoff Mice Using an Intravenous Self-Complementary Hexosaminidase Vector
Current Gene Therapy