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
-
Peniciketal A, A Novel Spiroketal Compound, Exerts Anticancer Effects by Inhibiting Cell Proliferation, Migration and Invasion of A549 Lung Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Targeting Prostate Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Natural and Synthetic Retinoids: Structural Bases and Biological Effects of Potential Clinical Relevance for the Prevention and Treatment of Infection-Driven Tumors
Anti-Infective Agents in Medicinal Chemistry Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-Induced Parkinsonism
Protein & Peptide Letters Detection of Squamous Cell Carcinoma Antigen with Micro- and Nanogap Interdigitated Electrodes and Gold Nanoparticles
Micro and Nanosystems Gold Nanoparticles as Carrier(s) for Drug Targeting and Imaging
Pharmaceutical Nanotechnology Combination of DC Vaccine and Conventional Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Folate Deficiency and Aberrant Expression of DNA Methyltransferase 1 were Associated with Cervical Cancerization
Current Pharmaceutical Design Peptide Nucleic Acids with a Structurally Biased Backbone. Updated Review and Emerging Challenges
Current Topics in Medicinal Chemistry Application of Mesenchymal Stem Cells in the Targeted Gene Therapy for Gastric Cancer
Current Stem Cell Research & Therapy A Comprehensive Study of Pharmacological Behaviors, Nano-Formulations, and Applications of Rosemary
The Natural Products Journal Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents
Mini-Reviews in Medicinal Chemistry (Neuro)Transmitter Systems in Circulating Immune Cells: A Target of Immunopharmacological Interventions?
Current Medicinal Chemistry Novel Anti-Angiogenic Compounds for Application in Tumor Therapy – COP9 Signalosome-Associated Kinases as Possible Targets
Mini-Reviews in Medicinal Chemistry Co-delivery of Plasmid DNA and Antisense Oligodeoxyribonucleotide into Human Carcinoma Cells by Cationic Liposomes
Current Pharmaceutical Biotechnology Manipulation of Dendritic Cells for Tumor Immunity
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Lipid Nucleoside Conjugates for the Treatment of Cancer
Current Pharmaceutical Design Syntheses and Preliminary Evaluation of Dual Target PET Probe [<sup>18</sup>F]-NOTA-Gly3- E (2PEG4-RGD-WH701) for PET Imaging of Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Gain of Function Effects of Z Alpha-1 Antitrypsin
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Himalayan Plants as a Source of Anti-Cancer Agents: A Review
The Natural Products Journal