Murph Mandi, Mills Gordon B
Department of Systems Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Expert Rev Mol Med. 2007 Oct 15;9(28):1-18. doi: 10.1017/S1462399407000476.
The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), the enzymes that generate and degrade them, and the receptors that receive their signals are all potential therapeutic targets in cancer. LPA and S1P signalling pathways can modulate a range of cellular processes that contribute to tumourigenesis, such as proliferation and motility, and components of the signalling pathways often show aberrant expression and altered activity upon malignant transformation. This article reviews LPA- and S1P-mediated activities that might contribute to the aetiology of cancer, and examines the potential of the many antagonists that have been developed to inhibit LPA and S1P signalling pathways. In addition, the outcomes of various clinical trials using LPA- and S1P-associated targets in cancer and other diseases are described, and future directions are discussed.
生物活性脂质溶血磷脂酸（LPA）和1-磷酸鞘氨醇（S1P）、生成和降解它们的酶以及接收其信号的受体，都是癌症潜在的治疗靶点。LPA和S1P信号通路可调节一系列促成肿瘤发生的细胞过程，如增殖和迁移，并且信号通路的组分在恶性转化时常常表现出异常表达和活性改变。本文综述了可能促成癌症病因的LPA和S1P介导的活性，并研究了已开发的许多抑制LPA和S1P信号通路的拮抗剂的潜力。此外，还描述了在癌症和其他疾病中使用LPA和S1P相关靶点的各种临床试验的结果，并讨论了未来的方向。
