Abstract
It has been approximately ten years since the Food and Drug Administration (FDA) approved paclitaxel for the treatment of platinum resistant epithelial ovarian carcinoma. Since the approval, the drug has found therapeutic applications in a variety of schedules and in a wide variety of epithelial malignancies. Its novel mechanism of action provided the hope that it would demonstrate anti-neoplastic activity in multidrug resistant tumor cells. Unfortunately, as with other chemotherapeutic drugs, resistance is commonly seen. Laboratory investigation has defined a wide variety of resistance mechanisms including overexpression of multidrug resistance (MDR-1) gene, molecular changes in the target molecule (β-tubulin), changes in apoptotic regulatory and mitosis checkpoint proteins, and more recently changes in lipid composition and potentially the overexpression of interleukin 6 (IL-6). This review describes the in vitro molecular data that define and support the various mechanisms of resistance and critically evaluates the evidence for the participation of these mechanisms in clinically relevant paclitaxel resistance. This review also explores pharmacologic attempts to modulate paclitaxel resistance, principally through inhibition of the MDR-1 drug efflux pump. Future avenues for drug resistance research and its pharmacologic manipulation in the clinic are discussed.
Keywords: paclitaxel, drug resistance, reversal of drug resistance, in vivo drug resistance assays, mdr, pgp, tubulin, cytokine
Current Cancer Drug Targets
Title: Paclitaxel Resistance: Molecular Mechanisms and Pharmacologic Manipulation
Volume: 3 Issue: 1
Author(s): R. Z. Yusuf, Z. Duan, D. E. Lamendola, R. T. Penson and M. V. Seiden
Affiliation:
Keywords: paclitaxel, drug resistance, reversal of drug resistance, in vivo drug resistance assays, mdr, pgp, tubulin, cytokine
Abstract: It has been approximately ten years since the Food and Drug Administration (FDA) approved paclitaxel for the treatment of platinum resistant epithelial ovarian carcinoma. Since the approval, the drug has found therapeutic applications in a variety of schedules and in a wide variety of epithelial malignancies. Its novel mechanism of action provided the hope that it would demonstrate anti-neoplastic activity in multidrug resistant tumor cells. Unfortunately, as with other chemotherapeutic drugs, resistance is commonly seen. Laboratory investigation has defined a wide variety of resistance mechanisms including overexpression of multidrug resistance (MDR-1) gene, molecular changes in the target molecule (β-tubulin), changes in apoptotic regulatory and mitosis checkpoint proteins, and more recently changes in lipid composition and potentially the overexpression of interleukin 6 (IL-6). This review describes the in vitro molecular data that define and support the various mechanisms of resistance and critically evaluates the evidence for the participation of these mechanisms in clinically relevant paclitaxel resistance. This review also explores pharmacologic attempts to modulate paclitaxel resistance, principally through inhibition of the MDR-1 drug efflux pump. Future avenues for drug resistance research and its pharmacologic manipulation in the clinic are discussed.
Export Options
About this article
Cite this article as:
Yusuf Z. R., Duan Z., Lamendola E. D., Penson T. R. and Seiden V. M., Paclitaxel Resistance: Molecular Mechanisms and Pharmacologic Manipulation, Current Cancer Drug Targets 2003; 3 (1) . https://dx.doi.org/10.2174/1568009033333754
DOI https://dx.doi.org/10.2174/1568009033333754 |
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
-
Lipid Nanoparticles for the Delivery of Biopharmaceuticals
Current Pharmaceutical Biotechnology MicroRNAs in Cancer Therapy: From Bench to Bedside
Current Cancer Therapy Reviews Editorial (A Significant Step Towards New Altitude)
Current Molecular Medicine Insulin Resistance and Alzheimers Disease: Molecular Links & Clinical Implications
Current Alzheimer Research Pharmacological Approaches of Neurofibrillary Degeneration
Current Alzheimer Research Acetylcholine Receptors and Tau Phosphorylation
Current Molecular Medicine Dimebon Attenuates the Aβ-Induced Mitochondrial Permeabilization
Current Alzheimer Research Beyond Hemostasis: The Role of Platelets in Inflammation, Malignancy and Infection
Cardiovascular & Hematological Disorders-Drug Targets Subject Index to Volume 3
Current Drug Targets - CNS & Neurological Disorders Rationale for the Development of Cholinesterase Inhibitors as Anti- Alzheimer Agents
Current Pharmaceutical Design A Cationic Gallium Phthalocyanine Inhibits Amyloid β Peptide Fibril Formation
Current Alzheimer Research Anticancer Peptides and Proteins: A Panoramic View
Protein & Peptide Letters From Anti-allergic to Anti-Alzheimer ’ s: Molecular Pharmacology of Dimebon™
Current Alzheimer Research The Role of Vasopressin in Affective Disorders: Possible Targets of Intervention
Central Nervous System Agents in Medicinal Chemistry Targeting the Endocannabinod System to Limit Myocardial and Cerebral Ischemic and Reperfusion Injury
Current Pharmaceutical Biotechnology Activin and TGF-β Effects on Brain Development and Neural Stem Cells
CNS & Neurological Disorders - Drug Targets Mechanisms of Melatonin in Alleviating Alzheimer’s Disease
Current Neuropharmacology Modulation of TRAIL-Induced Apoptosis by HDAC Inhibitors
Current Cancer Drug Targets bHLH Transcription Factors Inhibitors for Cancer Therapy: General Features for In Silico Drug Design
Current Medicinal Chemistry Non-Analgesic Effects of Opioids: Neuroprotection in the Retina
Current Pharmaceutical Design