Abstract
ATP-binding cassette (ABC) transporters are a large family of proteins implicated in physiological cellular functions. Selected components of the family play a well-recognized role in extruding conventional cytotoxic antitumor agents and molecularly targeted drugs from cells. Some lines of evidence also suggest links between transporters and tumor cell survival, in part unrelated to efflux. However, the study of the precise mechanisms regulating the function of drug transporters (e.g., posttranslational modifications such as glycosylation) is still in its infancy. A better definition of the molecular events clarifying the regulation of transporter levels including regulation by microRNAs may contribute to provide new molecular tools to target such a family of transporters. The present review focuses on the biological aspects that implicate ABC transporters in resistance of tumor cells, including cancer stem cells. Molecular analysis of well-known preclinical systems as well as of cancer stem cell models supports the notion that ABC transporters represent amenable targets for modulation of the efficacy of antitumor agents endowed with different molecular features. Recent achievements regarding tumor cell biology are expected to provide a rationale for developing novel inhibitors that target ABC transporters implicated in drug resistance.
Keywords: ABC transporters, cancer stem cells, drug resistance, drug targets, glycosylation, miRNAs, P-gp, BCRP, MRP, transporter inhibitor
Current Medicinal Chemistry
Title: Novel Insights into Targeting ATP-Binding Cassette Transporters for Antitumor Therapy
Volume: 18 Issue: 27
Author(s): L. Gatti, G. Cossa, G. L. Beretta, N. Zaffaroni and P. Perego
Affiliation:
Keywords: ABC transporters, cancer stem cells, drug resistance, drug targets, glycosylation, miRNAs, P-gp, BCRP, MRP, transporter inhibitor
Abstract: ATP-binding cassette (ABC) transporters are a large family of proteins implicated in physiological cellular functions. Selected components of the family play a well-recognized role in extruding conventional cytotoxic antitumor agents and molecularly targeted drugs from cells. Some lines of evidence also suggest links between transporters and tumor cell survival, in part unrelated to efflux. However, the study of the precise mechanisms regulating the function of drug transporters (e.g., posttranslational modifications such as glycosylation) is still in its infancy. A better definition of the molecular events clarifying the regulation of transporter levels including regulation by microRNAs may contribute to provide new molecular tools to target such a family of transporters. The present review focuses on the biological aspects that implicate ABC transporters in resistance of tumor cells, including cancer stem cells. Molecular analysis of well-known preclinical systems as well as of cancer stem cell models supports the notion that ABC transporters represent amenable targets for modulation of the efficacy of antitumor agents endowed with different molecular features. Recent achievements regarding tumor cell biology are expected to provide a rationale for developing novel inhibitors that target ABC transporters implicated in drug resistance.
Export Options
About this article
Cite this article as:
Gatti L., Cossa G., L. Beretta G., Zaffaroni N. and Perego P., Novel Insights into Targeting ATP-Binding Cassette Transporters for Antitumor Therapy, Current Medicinal Chemistry 2011; 18 (27) . https://dx.doi.org/10.2174/092986711797189682
DOI https://dx.doi.org/10.2174/092986711797189682 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
- Announcements
Related Articles
-
Marine Natural Products as a Promising Source of Therapeutic Compounds to Target Cancer Stem Cells
Current Medicinal Chemistry Application of Spray-drying and Electrospraying/Electospinning for Poorly Watersoluble Drugs: A Particle Engineering Approach
Current Pharmaceutical Design Medicinal Compound Celastrol As a Potential Clinical Anticancer Drug: Lessons Learned From Preclinical Studies
Clinical Cancer Drugs Evaluation of Biological Effects and Toxicity of Cetyltrimethylammonium Bromide Stabilized Silver Nanoparticles and Cetyltrimethylammonium Bromide Alone Following Intravenous Injection in Mice
Current Nanomedicine Current Advances in Delivery of Biotherapeutics Across the Blood-Brain Barrier
Current Drug Discovery Technologies BRAF Inhibitor Therapy for Melanoma, Thyroid and Colorectal Cancers: Development of Resistance and Future Prospects
Current Cancer Drug Targets TNF α Signaling Beholds Thalidomide Saga: A Review of Mechanistic Role of TNF-α Signaling Under Thalidomide
Current Topics in Medicinal Chemistry Uptake of [¹⁸F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter
Current Cancer Drug Targets Targeting PPARalpha in Alzheimer's Disease
Current Alzheimer Research Emerging Roles of microRNAs in the Molecular Responses to Hypoxia
Current Pharmaceutical Design State of the Art Molecular Pharmacology, Pathogenesis and Epigenetics of 3 Major Cancers: Lung Cancer, Ovarian Cancer, and Gliomas
Current Molecular Pharmacology Anti-Inflammatory Effects of Intravenous Anesthetics on Endotoxemia
Mini-Reviews in Medicinal Chemistry Natural Products in Structure-Assisted Design of Molecular Cancer Therapeutics
Current Pharmaceutical Design C-11 Radiochemistry in Cancer Imaging Applications
Current Topics in Medicinal Chemistry Hyaluronic Acid/Parecoxib-Loaded PLGA Microspheres for Therapy of Temporomandibular Disorders
Current Drug Delivery Blood Brain Barrier in Hypoxic-Ischemic Conditions
Current Neurovascular Research Biochemical, Molecular and Epigenetic Mechanisms of Valproic Acid Neuroprotection
Current Molecular Pharmacology Annexins in the Central Nervous System: Are they Neuroprotective or Proapoptotic Agents?
Medicinal Chemistry Reviews - Online (Discontinued) Nanomedicine: Magnetic Nanoparticles and their Biomedical Applications
Current Medicinal Chemistry P53 Gene Therapy Sensitizes Resistant Breast Cancer Cells to Doxorubicin Chemotherapy
Drug Delivery Letters