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Microtubule-targeting agents are clinically successful due to both mitotic and interphase impairment of microtubule function
Affiliation:1. Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, 40225 Düsseldorf, Germany;2. Institute of Transfusion Medicine, University Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, German Red Cross Blood Service, Baden-Wuerttemberg — Hessen, Germany;3. Institute of Human Genetics, Würzburg, Germany;4. Department of Pediatric Hematology and Oncology, University Children''s Hospital, University of Bonn, Germany;5. Center for Chronic Immunodeficiency (CCI), University of Freiburg, Germany;6. Center of Pediatrics, University of Freiburg, Germany;1. Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States;2. Department of Chemistry, School of Arts and Science, University of Pennsylvania, Philadelphia, PA 19104, United States;3. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, United States
Abstract:Microtubules undergo continual dynamic changes in mitotic cells as the mitotic spindle forms and is broken down and in interphase cells where they play a central role in intracellular trafficking, cell signaling, cell migration, and angiogenesis. Compounds that target the microtubule have been hugely successful in the clinic as chemotherapeutics, and this success is likely due to their ability to target cells regardless of their cell cycle stage. Additionally, new generation antibody-conjugated microtubule-targeting agents are improving the targeting of these drugs to tumors. Microtubule-targeting agents have been shown to have anti-angiogenic and vascular-disrupting properties as well as effects on cellular migration, intracellular trafficking, and cell secretion. There are a number of these compounds in development that target the vasculature, and different formulations of clinically used drugs are being developed to take advantage of these anti-angiogenic properties. Microtubule-targeting agents have also been shown to have the potential to treat neurodegenerative diseases, such as Alzheimer’s disease. Thus, drugs that target the microtubule will continue to have a major impact in oncology not only as anti-mitotics but also as potent inhibitors of interphase functions, and in future may also prove to be effective in reducing the consequences of neurodegenerative disease.
Keywords:Microtubule-targeting agents  Interphase microtubules  Cancer  Anti-vascular  Anti-angiogenesis  Neurodegeneration
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