New approaches to targeting the actin cytoskeleton for chemotherapy.

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.

• Authors: Teresa T Bonello, Justine R Stehn, Peter W Gunning
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 1 Issue 7 Pg. 1311-31 (Oct 2009) ISSN: 1756-8927 [Electronic] England
• PMID: 21426105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

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

Topics

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