Abstract
Pleiotropic resistance of tumor cells to treatment remains one of the major obstacles for successful cure of cancer patients. Tumor cells may acquire multidrug resistance (MDR) in the course of exposure to various compounds that are used in modern anticancer therapy, including cytotoxic drugs and differentiating agents. Therefore, the recurrence of the disease after the initial treatment may be associated with establishment of secondary MDR in the residual tumor. This phenotype is frequently mediated by P-glycoprotein, an ATP-dependent transmembrane pump capable of effluxing numerous compounds out of the cell. In humans, P-glycoprotein is encoded by the MDR1 gene. Rapid increase of the steady-state level of the MDR1 mRNA in response to stress stimuli is the mechanism of acquisition of P-glycoprotein- mediated MDR in cancer cells. Thus, up-regulation of the MDR1 gene is regarded as part of cellular stress response. This review shows that block of mechanisms that regulate the MDR1 overexpression can prevent the emergence of MDR in tumor cells that expressed null-to-low levels of MDR1 mRNA or P-glycoprotein prior to treatment. In particular, the MDR1 activation can be abrogated by targeting cytoplasmic pathways of signal transduction as well as by interfering with transcriptional up-regulation.
Keywords: Multidrug resistance MDR, P-glycoprotein, MDR1 gene, kDa-glycoprotein, Protein Kinase PKC, Plasma Membrane-Active Agents, Nuclear factor Kappa B, Isoform, Polyamides, Single gene targeting
Current Drug Targets
Title: Signal Transduction Pathways and Transcriptional Mechanisms as Targets for Prevention of Emergence of Multidrug Resistance in Human Cancer Cells
Volume: 2 Issue: 1
Author(s): Alexander A. Shtil
Affiliation:
Keywords: Multidrug resistance MDR, P-glycoprotein, MDR1 gene, kDa-glycoprotein, Protein Kinase PKC, Plasma Membrane-Active Agents, Nuclear factor Kappa B, Isoform, Polyamides, Single gene targeting
Abstract: Pleiotropic resistance of tumor cells to treatment remains one of the major obstacles for successful cure of cancer patients. Tumor cells may acquire multidrug resistance (MDR) in the course of exposure to various compounds that are used in modern anticancer therapy, including cytotoxic drugs and differentiating agents. Therefore, the recurrence of the disease after the initial treatment may be associated with establishment of secondary MDR in the residual tumor. This phenotype is frequently mediated by P-glycoprotein, an ATP-dependent transmembrane pump capable of effluxing numerous compounds out of the cell. In humans, P-glycoprotein is encoded by the MDR1 gene. Rapid increase of the steady-state level of the MDR1 mRNA in response to stress stimuli is the mechanism of acquisition of P-glycoprotein- mediated MDR in cancer cells. Thus, up-regulation of the MDR1 gene is regarded as part of cellular stress response. This review shows that block of mechanisms that regulate the MDR1 overexpression can prevent the emergence of MDR in tumor cells that expressed null-to-low levels of MDR1 mRNA or P-glycoprotein prior to treatment. In particular, the MDR1 activation can be abrogated by targeting cytoplasmic pathways of signal transduction as well as by interfering with transcriptional up-regulation.
Export Options
About this article
Cite this article as:
Shtil A. Alexander, Signal Transduction Pathways and Transcriptional Mechanisms as Targets for Prevention of Emergence of Multidrug Resistance in Human Cancer Cells, Current Drug Targets 2001; 2 (1) . https://dx.doi.org/10.2174/1389450013348957
DOI https://dx.doi.org/10.2174/1389450013348957 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Structural and Mechanistic Bases of the Anticancer Activity of Natural Aporphinoid Alkaloids
Current Topics in Medicinal Chemistry Genetically Engineered Stem Cells for Therapeutic Gene Delivery
Current Gene Therapy Targeting Ion Channels in Leukemias: A New Challenge for Treatment
Current Medicinal Chemistry Microdialysis: A Technique for Pharmacokinetic-Pharmacodynamic Studies of Oncological Drugs
Current Pharmaceutical Biotechnology 9th International Meeting on Metabotropic Gglutamate Receptors (Taormina, Sicily, October 1-6, 2017).
Current Neuropharmacology The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension
Current Drug Discovery Technologies The Novel Functions of cGMP-Specific Phosphodiesterase 5 and its Inhibitors in Carcinoma Cells and Pulmonary/Cardiovascular Vessels
Current Topics in Medicinal Chemistry Synthesis and Biological Evaluation of Triazole-Vanillin Molecular Hybrids as Anti-Cancer Agents
Current Bioactive Compounds <i>Lophira alata</i> Suppresses Phorbol Ester-Mediated Increase in Cell Growth via Inhibition of Protein Kinase C-α/Akt in Glioblastoma Cells
Anti-Cancer Agents in Medicinal Chemistry The Potential of Tetrandrine Against Gliomas
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Gene Products Delivery by Neuron Stem Cells
Current Pharmaceutical Biotechnology Targeting the Akt-pathway to Improve Radiosensitivity in Glioblastoma
Current Pharmaceutical Design Antidepressant Desipramine Leads to C6 Glioma Cell Autophagy: Implication for the Adjuvant Therapy of Cancer
Anti-Cancer Agents in Medicinal Chemistry Nanoparticles: Functionalization and Multifunctional Applications in Biomedical Sciences
Current Medicinal Chemistry Regulators of Chemokine Receptor Activity as Promising Anticancer Therapeutics
Current Cancer Drug Targets Anticancer Drug Combinations, How Far We can Go Through?
Anti-Cancer Agents in Medicinal Chemistry Voltage-Dependent Potassium Channels Kv1.3 and Kv1.5 in Human Cancer
Current Cancer Drug Targets Technological Maturity and Systematic Review of Medicinal Plants with Pharmacological Activity in the Central Nervous System
Recent Patents on Biotechnology Nanomaterial Based Approaches for the Diagnosis and Therapy of Cardiovascular Diseases
Current Pharmaceutical Design HLA-G Expression in Cancers: Potential Role in Diagnosis, Prognosis and Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets