Targeting CDKN3 in cervical cancer

Expert Opin Ther Targets. 2014 Oct;18(10):1149-62. doi: 10.1517/14728222.2014.941808. Epub 2014 Aug 25.

Abstract

Introduction: The cyclin-dependent kinase inhibitor 3 gene (CDKN3), which is involved in mitosis, has been found upregulated and associated with low survival in cervical cancer (CC) patients. Therefore, as in other cancers, CDKN3 could be a potential target in CC.

Areas covered: In this review, the authors analyzed the evidence supporting the upregulation of CDKN3 in CC, its role in mitosis and the cell cycle, the evidence that CDKN3 may be useful as marker for survival and selection of CC patients for additional chemotherapy or specific target cancer therapy, the data supporting the role of CDKN3 in cell proliferation, and how CDKN3 targeting with specific small interfering RNA (siRNAs) suppress cell proliferation of cell lines derived from CC and other cancers. Finally, we discuss if the upregulation of CDKN3 can be part of the human papilloma virus strategy to avoid the mitosis checkpoint, the research to find small specific drugs to target CDKN3 and the advantages that CDKN3 has as target for novel drug design for CC treatment.

Expert opinion: CDKN3 might be useful not only as marker for survival and selection of CC patients for additional chemotherapy or specific target cancer therapy, but also as a potential target to develop specific small drugs to combat CC.

Keywords: cancer treatment; cancer-targeting genes; cervical cancer; cyclin-dependent kinase inhibitor 3 gene; gene expression; human papilloma virus; microarrays; mitosis.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase Inhibitor Proteins / genetics*
  • Drug Design
  • Dual-Specificity Phosphatases / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mitosis / physiology
  • Molecular Targeted Therapy
  • Survival Rate
  • Up-Regulation
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • CDKN3 protein, human
  • Dual-Specificity Phosphatases