title: Antimitotic drugs in cancer chemotherapy: promises and pitfalls.
abstract: Cancer cells usually display higher proliferation rates than normal cells. Some currently used antitumor drugs, such as vinca alkaloids and taxanes, act by targeting microtubules and inhibiting mitosis. In the last years, different mitotic regulators have been proposed as drug target candidates for antitumor therapies. In particular, inhibitors of Cdks, Chks, Aurora kinase and Polo-like kinase have been synthesized and evaluated in vitro and in animal models and some of them have reached clinical trials. However, to date, none of these inhibitors has been still approved for use in chemotherapy regimes. We will discuss here the most recent preclinical information on those new antimitotic drugs, as well as the possible molecular bases underlying their lack of clinical efficiency. Also, advances in the identification of other mitosis-related targets will be also summarized.
authors.affiliation: Departamento de Bioquimica y Biologia Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Spain. imarzo@unizar.es
authors.forename: Isabel
authors.initials: I
authors.lastname: Marzo
authors.forename: Javier
authors.initials: J
authors.lastname: Naval
mesh_terms: D050256:Antimitotic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011744:Pyrimidinones; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011744:Pyrimidinones; D011799:Quinazolines; C508757:ispinesib; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C549567:adavosertib
keywords: Cancer; Chemotherapy; Mitosis