Antimitotic agents for the treatment of patients with metastatic castrate-resistant prostate cancer

Michel D. Wissing, Paul J. Van Diest, Elsken Van Der Wall, Hans Gelderblom

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: 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. Areas covered: 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. Expert opinion: 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.

Original languageEnglish (US)
Pages (from-to)635-661
Number of pages27
JournalExpert Opinion on Investigational Drugs
Volume22
Issue number5
DOIs
StatePublished - May 1 2013

Keywords

  • Aurora kinases
  • Chemotherapy
  • Epothilone
  • Kinesin spindle protein
  • Metastatic castrate-resistant prostate cancer
  • Mitosis
  • Polo-like kinase 1
  • Taxane

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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