Tumor-specific nuclear targeting: promises for anti-cancer therapy?

Drug Resist Updat. Feb-Apr 2006;9(1-2):40-50. doi: 10.1016/j.drup.2006.02.003. Epub 2006 Apr 18.

Abstract

Recent developments in anti-cancer gene therapy suggest that the idea of a magic bullet for cancer may not be a pipe dream. Viral-based anti-cancer vectors for gene therapy have been used preferentially in this regard, but recent results from clinical trials have raised serious concerns as to their safety. For this reason, the development of non-viral vectors able to deliver drugs or suicide genes specifically to cancer cells is of paramount importance. In this context, great interest has been raised by recent reports that several proteins, including viral protein 3 (VP3 or Apoptin) from Chicken Anemia Virus, are capable of selectively killing tumor cells. Intriguingly, VP3's anti-cancer activity is strongly linked to its ability to localize more efficiently in the nucleus of cancer and transformed cells than that of normal, non-transformed cells with a tumor cell-specific nuclear targeting signal (tNTS) located at the C-terminus of the protein. Clearly, the VP3 tNTS is an exciting prospect to enhance non-viral-mediated cancer cell killing. This review will discuss recent advances in the understanding of the mechanism responsible for VP3 tumor-specific nuclear localization, including its specific phosphorylation, and the implications for the enhancement of anti-cancer therapy. It also proposes alternative strategies to develop tNTSs for anti-cancer therapies.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Apoptosis / physiology*
  • Capsid Proteins / metabolism
  • Capsid Proteins / physiology*
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Genes, Transgenic, Suicide / genetics
  • Genes, Transgenic, Suicide / physiology*
  • Genetic Therapy / methods*
  • Genetic Therapy / trends
  • Humans
  • Molecular Biology / trends*
  • Neoplasms / drug therapy
  • Neoplasms / therapy*
  • Photochemotherapy

Substances

  • Capsid Proteins
  • VP3 protein, Chicken anemia virus