Mitosis-targeted anti-cancer therapies: where they stand

Cell Death Dis. 2012 Oct 18;3(10):e411. doi: 10.1038/cddis.2012.148.

Abstract

The strategy of clinically targeting cancerous cells at their most vulnerable state during mitosis has instigated numerous studies into the mitotic cell death (MCD) pathway. As the hallmark of cancer revolves around cell-cycle deregulation, it is not surprising that antimitotic therapies are effective against the abnormal proliferation of transformed cells. Moreover, these antimitotic drugs are also highly selective and sensitive. Despite the robust rate of discovery and the development of mitosis-selective inhibitors, the unpredictable complexities of the human body's response to these drugs still herald the biggest challenge towards clinical success. Undoubtedly, the need to bridge the gap between promising preclinical trials and effective translational bedside treatment prompts further investigations towards mapping out the mechanistic pathways of MCD, understanding how these drugs work as medicine in the body and more comprehensive target validations. In this review, current antimitotic agents are summarized with particular emphasis on the evaluation of their clinical efficacy as well as their limitations. In addition, we discuss the basis behind the lack of activity of these inhibitors in human trials and the potential and future directions of mitotic anticancer strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphatases / metabolism
  • Anaphase-Promoting Complex-Cyclosome
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Mitosis / drug effects*
  • Molecular Motor Proteins / antagonists & inhibitors
  • Molecular Motor Proteins / metabolism
  • Multiprotein Complexes / antagonists & inhibitors
  • Multiprotein Complexes / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasms / drug therapy
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors
  • Ubiquitin-Protein Ligase Complexes / metabolism

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Molecular Motor Proteins
  • Multiprotein Complexes
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • condensin complexes
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Protein-Serine-Threonine Kinases
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases