RAC1: An Emerging Therapeutic Option for Targeting Cancer Angiogenesis and Metastasis

被引:214
作者
Bid, Hemant K. [1 ]
Roberts, Ryan D. [1 ]
Manchanda, Parmeet K. [2 ]
Houghton, Peter J. [1 ]
机构
[1] Nationwide Childrens Hosp, Ctr Childhood Canc, Columbus, OH 43205 USA
[2] Ohio State Univ, James Canc Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA
关键词
SMALL-MOLECULE INHIBITOR; RHO GTPASES; BREAST-CANCER; CELL-MIGRATION; TRASTUZUMAB RESISTANCE; SIGNALING PATHWAY; RATIONAL DESIGN; TUMOR; OSU-03012; MECHANISM;
D O I
10.1158/1535-7163.MCT-13-0164
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (c) 2013 AACR.
引用
收藏
页码:1925 / 1934
页数:10
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