New approaches to targeting the actin cytoskeleton for chemotherapy

Future Med Chem. 2009 Oct;1(7):1311-31. doi: 10.4155/fmc.09.99.

Abstract

The actin cytoskeleton is indispensable for normal cellular function. In particular, several actin-based structures coordinate cellular motility, a process hijacked by tumor cells in order to facilitate their propagation to distant sites. The actin cytoskeleton, therefore, represents a point for chemotherapeutic intervention. The challenge in disrupting the actin cytoskeleton is in preserving actin-driven contraction of cardiac and skeletal muscle. By targeting actin-binding proteins with altered expression in malignancy, it may be possible to achieve tumor-specific toxicity. A number of actin-binding proteins act cooperatively and synergistically to regulate actin structures required for motility. The actin cytoskeleton is characterized by a significant degree of plasticity. Targeting specific actin-binding proteins for chemotherapy will only be successful if no other compensatory mechanisms exist.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / drug effects*
  • Actin Cytoskeleton / physiology
  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism
  • Cortactin / genetics
  • Cortactin / metabolism
  • Destrin / genetics
  • Destrin / metabolism
  • Gelsolin / genetics
  • Gelsolin / metabolism
  • Humans
  • Microfilament Proteins / antagonists & inhibitors*
  • Microfilament Proteins / chemistry
  • Myosin Type II / genetics
  • Myosin Type II / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Signal Transduction
  • Tropomyosin / genetics
  • Tropomyosin / metabolism
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Cortactin
  • Destrin
  • Gelsolin
  • Microfilament Proteins
  • Tropomyosin
  • Wiskott-Aldrich Syndrome Protein Family
  • Myosin Type II