title: Antimitotic agents for the treatment of patients with metastatic castrate-resistant prostate cancer.
abstract: BACKGROUND
  Metastatic castrate-resistant prostate cancer (mCRPC) is the second deadliest cancer in men. The group of taxanes, which target microtubules of mitotic cells, is currently the only chemotherapy which has proven to increase overall survival in mCRPC patients. Other mitotic inhibitors are being explored for their clinical potential in mCRPC treatment.
  
  
  METHODS
  In this review, we summarize recent developments in the application of mitotic inhibitors for mCRPC from a clinical perspective. The four main groups of mitotic inhibitors currently being tested in clinical trials are microtubule-inhibitors, polo-like kinase 1 inhibitors, aurora kinase inhibitors and kinesin-spindle protein inhibitors. Compounds of these groups of inhibitors that are in clinical development for mCRPC are discussed. For this extensive overview, relevant literature was searched in PubMed and retrieved from clinicaltrials.gov and presentations at ASCO/AACR meetings.
  
  
  CONCLUSIONS
  In general, mitotic inhibitors are clinically well tolerated but exert limited antitumor activity compared to preclinical study results. However, efficacy of mitotic inhibitors is improving, either by personalizing treatment, by introducing more active compounds, by decreasing resistance of cancer cells against mitotic inhibitors or by using mitotic inhibitors in combination therapies.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2 K1-62, 2333ZA Leiden, The Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Wissing
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000627:therapeutic use*; D064127:Aurora Kinases; D002369:Castration; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use; D000097869:Polo-Like Kinase 1
chemical_list: D050256:Antimitotic Agents; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D016547:Kinesins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D000097869:Polo-Like Kinase 1; C470243:KIF11 protein, human