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
-
The Therapeutic Potential of Sigma (σ) Receptors for the Treatment of Central Nervous System Diseases: Evaluation of the Evidence
Current Pharmaceutical Design Role of Autophagy in Alzheimer’s Disease
Current Enzyme Inhibition Early Development of Sea Urchin P.lividus Under Static (6 mT) and Pulsed Magnetic Fields (15 and 72 Hz)
Current Chemical Biology Effect of DNA Repair Deficiencies on the Cytotoxicity of Drugs Used in Cancer Therapy - A Review
Current Medicinal Chemistry Hepatocyte Growth Factor and Insulin-like Growth Factor-1 based Cellular Therapies for Oxidative Stress Injury
Current Stem Cell Research & Therapy 1, 2-Benzisoxazole: A Privileged Structure with a Potential for Polypharmacology
Current Pharmaceutical Design Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94
Current Topics in Medicinal Chemistry Multi-Target Strategy and Experimental Studies of Traditional Chinese Medicine for Alzheimer’s Disease Therapy
Current Topics in Medicinal Chemistry MDM2 Inhibitors for Pancreatic Cancer Therapy
Mini-Reviews in Medicinal Chemistry The Therapeutic Value of Natural Agents to Treat miRNA Targeted Breast Cancer in African-American and Caucasian-American Women
Current Drug Targets Neurotrophic Factor Treatment After Spinal Root Avulsion Injury
Central Nervous System Agents in Medicinal Chemistry DYRK1A: A Potential Drug Target for Multiple Down Syndrome Neuropathologies
CNS & Neurological Disorders - Drug Targets Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells
Anti-Cancer Agents in Medicinal Chemistry Emerging RNA-based Drugs: siRNAs, microRNAs and Derivates
Central Nervous System Agents in Medicinal Chemistry Establishing Genomic/Transcriptomic Links Between Alzheimer’s Disease and Type 2 Diabetes Mellitus by Meta-Analysis Approach
CNS & Neurological Disorders - Drug Targets TRAIL as Biomarker and Potential Therapeutic Tool for Cardiovascular Diseases
Current Drug Targets MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion
Current Medicinal Chemistry Exploring the Anti-Neuroinflammatory Potential of Steroid and Terpenoid-Derived Phytochemicals to Combat Alzheimer's Disease
Current Pharmaceutical Design Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
Current Drug Targets Hedgehog Signaling and Urological Cancers
Current Drug Targets