Microtubule-targeting agents are clinically successful due to both mitotic and interphase impairment of microtubule function

Jessica J. Field, Arun Kanakkanthara, John H. Miller

Research output: Contribution to journalReview article

106 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5050-5059
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number18
DOIs
StatePublished - Sep 15 2015

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Keywords

  • Anti-angiogenesis
  • Anti-vascular
  • Cancer
  • Interphase microtubules
  • Microtubule-targeting agents
  • Neurodegeneration

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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