Abstract
Background: The ultimate emergence of multidrug resistance remains a severe limitation of chemotherapy treatment for patients with cancer. The best-characterized cause of drug resistance involves the overexpression of P-glycoprotein (Pgp), which decreases the intracellular accumulation of chemotherapeutic agents in drug-resistant cancer cells. Thus, Pgp has become an attractive potential target for treating chemotherapy-resistant cancer, but the outcomes of using chemotherapy in combination with Pgp inhibitors in clinical trials to date have been disappointing.
Objective: We herein examine the relationship between Pgp and drug resistance and update the strategies for overcoming drug resistance by targeting Pgp, with a special focus on the recent progress in the area of preventing the development of drug resistance by targeting Pgp both in vitro and in vivo. Given the essential roles of drug-resistant cancer models in these investigations, commonly used approaches for establishing drug-resistant models in the laboratory are also addressed.
Conclusion: Considering the roles of Pgp in normal physiological conditions and its appreciated roles in detoxification, the currently available Pgp inhibitors undoubtedly cannot be used to reverse drug resistance in the clinic. Although agents that target Pgp to prevent and/or reverse drug resistance are not beneficial at the doses used in the laboratory when administered to patients with cancer who are enrolled in clinical trials, compounds targeting Pgp are widely acknowledged to be promising for circumventing drug resistance.
Keywords: Multidrug resistance, P-glycoprotein, P-glycoprotein inhibitor, drug resistant models establishment.
Current Cancer Drug Targets
Title:An Update on Circumventing Multidrug Resistance in Cancer by Targeting P-Glycoprotein
Volume: 18 Issue: 7
Author(s): Xiaoqian Yang, Xiaoduan Li, Zhenfeng Duan and Xipeng Wang*
Affiliation:
- Department of Gynecology and Obstetrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092,China
Keywords: Multidrug resistance, P-glycoprotein, P-glycoprotein inhibitor, drug resistant models establishment.
Abstract: Background: The ultimate emergence of multidrug resistance remains a severe limitation of chemotherapy treatment for patients with cancer. The best-characterized cause of drug resistance involves the overexpression of P-glycoprotein (Pgp), which decreases the intracellular accumulation of chemotherapeutic agents in drug-resistant cancer cells. Thus, Pgp has become an attractive potential target for treating chemotherapy-resistant cancer, but the outcomes of using chemotherapy in combination with Pgp inhibitors in clinical trials to date have been disappointing.
Objective: We herein examine the relationship between Pgp and drug resistance and update the strategies for overcoming drug resistance by targeting Pgp, with a special focus on the recent progress in the area of preventing the development of drug resistance by targeting Pgp both in vitro and in vivo. Given the essential roles of drug-resistant cancer models in these investigations, commonly used approaches for establishing drug-resistant models in the laboratory are also addressed.
Conclusion: Considering the roles of Pgp in normal physiological conditions and its appreciated roles in detoxification, the currently available Pgp inhibitors undoubtedly cannot be used to reverse drug resistance in the clinic. Although agents that target Pgp to prevent and/or reverse drug resistance are not beneficial at the doses used in the laboratory when administered to patients with cancer who are enrolled in clinical trials, compounds targeting Pgp are widely acknowledged to be promising for circumventing drug resistance.
Export Options
About this article
Cite this article as:
Yang Xiaoqian, Li Xiaoduan , Duan Zhenfeng and Wang Xipeng *, An Update on Circumventing Multidrug Resistance in Cancer by Targeting P-Glycoprotein, Current Cancer Drug Targets 2018; 18 (7) . https://dx.doi.org/10.2174/1568009617666170623114524
DOI https://dx.doi.org/10.2174/1568009617666170623114524 |
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
-
Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Current Pharmaceutical Design Identification of Disease-Relevant Genes for Molecularly-Targeted Drug Discovery
Current Cancer Drug Targets Recent Advancements in Nanodiamond Mediated Brain Targeted Drug Delivery and Bioimaging of Brain Ailments: A Holistic Review
Pharmaceutical Nanotechnology Graphene Oxide: A Carrier for Pharmaceuticals and a Scaffold for Cell Interactions
Current Topics in Medicinal Chemistry A New Approach for Skin-Derived Precursors to Ameliorate Skin Photodamage Through Activation of Nrf2 Signaling Pathway
Current Signal Transduction Therapy HSP27: Mechanisms of Cellular Protection Against Neuronal Injury
Current Molecular Medicine CD95 Signaling in Cancer Treatment
Current Pharmaceutical Design CNS Immune Surveillance and Neuroinflammation: Endocannabinoids Keep Control
Current Pharmaceutical Design Dysregulation of Neurotrophic and Haematopoietic Growth Factors in Alzheimer’s Disease: From Pathophysiology to Novel Treatment Strategies
Current Alzheimer Research The Return of the INGs, Histone Mark Sensors and Phospholipid Signaling Effectors
Current Drug Targets Boron Nitride Nanotubes: Production, Properties, Biological Interactions and Potential Applications as Therapeutic Agents in Brain Diseases
Current Nanoscience Targeting the AKT Pathway in Glioblastoma
Current Pharmaceutical Design MET and ALK as Targets for the Treatment of NSCLC
Current Pharmaceutical Design Molecular Markers of Glioblastoma and the Potential for Integration with Imaging: the Future for Assigning Prognosis and Best Treatment Strategy
Current Molecular Imaging (Discontinued) Cell-penetrating Peptide-based Intelligent Liposomal Systems for Enhanced Drug Delivery
Current Pharmaceutical Biotechnology Gene Therapy and Cell Reprogramming For the Aging Brain: Achievements and Promise
Current Gene Therapy Role of ABC Transporters in the Chemoresistance of Human Gliomas
Current Cancer Drug Targets Glioblastoma: Prognostic Factors and Predictive Response to Radio and Chemotherapy
Current Medicinal Chemistry Polyethylenimine as a Promising Vector for Targeted siRNA Delivery
Current Clinical Pharmacology The Rationale of Targeting Neutrophils with Dapsone during Glioblastoma Treatment
Anti-Cancer Agents in Medicinal Chemistry