title: Mitosis is not a key target of microtubule agents in patient tumors.
abstract: Mitosis-specific agents have, to date, not been clinically successful. By contrast, microtubule-targeting agents (MTAs) have a long record of success, usually attributed to the induction of mitotic arrest. Indeed, it was this success that led to the search for mitosis-specific inhibitors. We believe the clinical disappointment of mitosis-specific inhibitors stands as evidence that MTAs have been successful not only by interfering with mitosis but, more importantly, by disrupting essential interphase cellular mechanisms. In this Perspective we will review literature that supports a paradigm shift in how we think about one of our most widely used classes of chemotherapeutics-MTAs. We believe that the steady presence and constant physiological role of microtubules are responsible for the overall success of MTAs. While mitosis-specific inhibitors are effective on only a small fraction of the tumor mass (dividing cells), MTAs target tubulin, a protein that has crucial roles in both mitotic and non-mitotic cells.
authors.affiliation: National Cancer Institute, National Institutes of Health, Building 10, 10 Center Drive, Bethesda, MD 20892, USA. komlodie@mail.nih.gov
authors.forename: Edina
authors.initials: E
authors.lastname: Komlodi-Pasztor
authors.forename: Dan
authors.initials: D
authors.lastname: Sackett
authors.forename: Julia
authors.initials: J
authors.lastname: Wilkerson
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
mesh_terms: D050256:Antimitotic Agents / Q000627:therapeutic use*; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D050256:Antimitotic Agents