RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis.
Angiogenesis and metastasis are well recognized as processes fundamental to the development of malignancy. Both processes involve the coordination of multiple cellular and chemical activities through myriad signaling networks, providing a mass of potential targets for therapeutic intervention. This review will focus on one master regulator of cell motility, RAC1, and the existing data with regard to its role in cell motility, including particular roles for tumor angiogenesis and invasion/metastasis. We also emphasize the preclinical investigations carried out with RAC1 inhibitors to evaluate the therapeutic potential of this target. Herein, we explore potential future directions as well as the challenges of targeting RAC1 in the treatment of cancer. Recent insights at the molecular and cellular levels are paving the way for a more directed and detailed approach to target mechanisms of RAC1 regulating angiogenesis and metastasis. Understanding these mechanisms may provide insight into RAC1 signaling components as alternative therapeutic targets for tumor angiogenesis and metastasis.
Corresponding Author: Peter J. Houghton, Center for Childhood Cancer, The Research Institute, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205. Peter.Houghton@nationwidechildrens.org.
Hemant K
HK
Bid
Ryan D
RD
Roberts
Parmeet K
PK
Manchanda
Peter J
PJ
Houghton
D002465:Cell Movement / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics*; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein