Novel approaches in anti-angiogenic treatment targeting endothelial F-actin: a new anti-angiogenic strategy?
As a functional blood supply is crucial for growth of solid tumors, the development of anticancer agents to inhibit the formation of new tumor blood vessels is an area of extensive research. Endothelial cell motility driven by the dynamics of the cytoskeleton is a key feature of angiogenesis. Agents that preferentially target endothelial tubulin are well established, and inhibition of the endothelial actin dynamics appears to be another promising anti-angiogenic strategy. Remodeling of the actin cytoskeleton is regulated by several pathways involving a large number of signaling proteins. Therefore, therapeutic strategies for the modulation of actin dynamics include agents that target the actin cytoskeleton directly, as well as inhibitors of actin binding proteins and regulators in upstream pathways. This review provides an overview of the regulation of the actin cytoskeleton and proteins that could potentially be targeted by therapeutic agents. In addition, an outline of promising agents, which includes recombinant proteins, endogenous effectors and treatment regimes that exert anti-angiogenic effects partly mediated by affecting endothelial actin dynamics is provided.
Thoenes
Lilja
L
Ludwig-Maximilian-Universität, Pharmaceutical Biology-Biotechnology, Butenandtstrasse 5-13, D-81377 Munich, Germany.
Günther
Michael
M
D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000199:Actins; D020533:Angiogenesis Inhibitors; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D024462:Myosin Type II