Abstract
Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also describes the drugs that are substrates of these proteins. The usefulness of animal and cellular models to evaluate the role of these transporters on the uptake and efflux of anticancer drugs is discussed. Finally, the results of preclinical and clinical studies about the utility of some inhibitors of these pumps, as well as the implications of polymorphism of ABC transporters on the efficacy and safety of anticancer therapeutics are reported.
Keywords: abc (atp binding cassette) transporters, abcg2 transporter (atp-binding cassette transporter placentaspecific, abcp, breast cancer resistance protein, bcrp, and mitoxantrone-resistance protein, mrx), anticancer therapeutics, multidrug resistance (mdr), modulation of mdr
Current Drug Delivery
Title: Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
Volume: 1 Issue: 3
Author(s): V. Merino, N. V. Jiménez-Torres and M. Merino-Sanjuan
Affiliation:
Keywords: abc (atp binding cassette) transporters, abcg2 transporter (atp-binding cassette transporter placentaspecific, abcp, breast cancer resistance protein, bcrp, and mitoxantrone-resistance protein, mrx), anticancer therapeutics, multidrug resistance (mdr), modulation of mdr
Abstract: Variations in drug uptake and efflux, as well as changes in intracellular drug entrapment and distribution may represent important resistance mechanisms to cancer therapy. A variety of ATP binding cassette transporters (ABC) localised in multiple cell membranes is implied in those phenomena, representing a mechanism of protection of cells against xenobiotics. Many cancer cell lines over express some ABC transporters, especially p-glycoprotein, MRP1 and BCRP. This over expression is related to worse cancer treatment outcome and, in some cases, reduced overall survival of cancer patients. This paper reviews the location and physiological role of the three transporters mentioned and also describes the drugs that are substrates of these proteins. The usefulness of animal and cellular models to evaluate the role of these transporters on the uptake and efflux of anticancer drugs is discussed. Finally, the results of preclinical and clinical studies about the utility of some inhibitors of these pumps, as well as the implications of polymorphism of ABC transporters on the efficacy and safety of anticancer therapeutics are reported.
Export Options
About this article
Cite this article as:
Merino V., Jiménez-Torres V. N. and Merino-Sanjuan M., Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy, Current Drug Delivery 2004; 1 (3) . https://dx.doi.org/10.2174/1567201043334650
DOI https://dx.doi.org/10.2174/1567201043334650 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...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
-
Physiological Roles of Neuronal Nicotinic Receptors Subtypes: New Insights on the Nicotinic Modulation of Neurotransmitter Release, Synaptic Transmission and Plasticity
Current Topics in Medicinal Chemistry Regulation of P2X3 Receptor Structure and Function
CNS & Neurological Disorders - Drug Targets Transcriptome Analysis of FEN1 Knockdown HEK293T Cell Strain Reveals Alteration in Nucleic Acid Metabolism, Virus Infection, Cell Morphogenesis and Cancer Development
Combinatorial Chemistry & High Throughput Screening Nanostructured Therapeutic Systems of PUFAs for the Treatment of Glioblastoma Multiforme
Current Drug Metabolism MicroRNA Levels in Cervical Cancer Samples and Relationship with Lesion Grade and HPV Infection
MicroRNA New Insights into HLA-G and Inflammatory Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Expression of Defensins in Gingiva and Their Role in Periodontal Health and Disease
Current Pharmaceutical Design Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Human Papillomavirus (HPV) Vaccines as an Option for Preventing Cervical Malignancies: (How) Effective and Safe?
Current Pharmaceutical Design The Association between Tumor-associated Macrophages and Glioblastoma: A Potential Target for Therapy
Current Pharmaceutical Design Potentials of Hydrogels in Cancer Therapy
Current Cancer Therapy Reviews Fibrates in the Chemical Action of Daunorubicin
Current Cancer Drug Targets Integrative Approaches for microRNA Target Prediction: Combining Sequence Information and the Paired mRNA and miRNA Expression Profiles
Current Bioinformatics Antitumor Activity of Zinc Nanoparticles Synthesized with Berberine on Human Epithelial Colorectal Adenocarcinoma (Caco-2) Cells through Acting on Cox-2/NF-kB and p53 Pathways
Anti-Cancer Agents in Medicinal Chemistry Tracking Cell Signaling Protein Expression and Phosphorylation by Innovative Proteomic Solutions
Current Pharmaceutical Biotechnology FoxO1 Inhibitors: The Future Medicine for Metabolic Disorders?
Current Diabetes Reviews Spectroscopic and Theoretical Approaches for the Determination of Heparin Saccharide Structure and the Study of Protein-Glycosaminoglycan Complexes in Solution
Current Medicinal Chemistry Functional Interplay between RNA-Binding Protein HuR and microRNAs
Current Protein & Peptide Science Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions
Current Medicinal Chemistry Targeting CSCs in Tumor Microenvironment: The Potential Role of ROS-Associated miRNAs in Tumor Aggressiveness
Current Stem Cell Research & Therapy