Corresponding Author: Peter J. Houghton, Center for Childhood Cancer, The Research Institute, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205.
Mol Cancer Ther. 2013 Oct;12(10):1925-34. doi: 10.1158/1535-7163.MCT-13-0164. Epub 2013 Sep 26.
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.
血管生成和转移是公认的恶性肿瘤发展的基本过程。这两个过程都涉及通过无数信号网络协调多种细胞和化学活动,为治疗干预提供了大量潜在的靶点。这篇综述将集中讨论一种细胞运动的主要调节因子 RAC1,以及关于其在细胞运动中的作用的现有数据,包括肿瘤血管生成和侵袭/转移的特定作用。我们还强调了用 RAC1 抑制剂进行的临床前研究,以评估该靶点的治疗潜力。在这里,我们探讨了靶向 RAC1 治疗癌症的潜在未来方向和挑战。在分子和细胞水平的最新见解为更有针对性和详细的方法来靶向 RAC1 调节血管生成和转移的机制铺平了道路。了解这些机制可能为 RAC1 信号传导成分作为肿瘤血管生成和转移的替代治疗靶点提供了一些思路。