Department of Investigational Cancer Therapeutics, The Phase I Clinical Trials Program, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Future Oncol. 2010 Jun;6(6):885-91. doi: 10.2217/fon.10.71.
The Ras family of genes is involved in the cellular regulation of proliferation, differentiation, cell adhesion and apoptosis. The K-ras gene is mutated in over 90% of pancreatic cancer cases. Salirasib (S-trans,trans-farnesylthiosalycilic acid [FTS]) is a synthetic small molecule that acts as a potent Ras inhibitor. It is a farnesylcysteine mimetic that selectively disrupts the association of active RAS proteins with the plasma membrane. Animal studies demonstrated that salirasib inhibited tumor growth, downregulated gene expression in the cell cycle and Ras signaling pathways. In a clinical study of salirasib combined with standard doses of gemcitabine, it was demonstrated that the two drugs have no overlapping pharmacokinetics. The salirasib recommended dose was 600 mg twice daily and the progression-free survival was 4.7 months. Future studies will determine whether salirasib adds to the anti-tumor activity of drugs approved by the US FDA for pancreatic cancer.
Ras 家族基因参与细胞增殖、分化、细胞黏附和细胞凋亡的调控。K-ras 基因在超过 90%的胰腺癌病例中发生突变。Salirasib（S-反式，反式-法呢基硫代水杨酸[FTS]）是一种合成的小分子，可作为有效的 Ras 抑制剂。它是一种法尼基半胱氨酸类似物，可选择性破坏活性 Ras 蛋白与质膜的结合。动物研究表明，salirasib 可抑制肿瘤生长，下调细胞周期和 Ras 信号通路中的基因表达。在一项关于 salirasib 联合标准剂量吉西他滨的临床研究中，证明两种药物没有重叠的药代动力学。salirasib 的推荐剂量为每天两次 600mg，无进展生存期为 4.7 个月。未来的研究将确定 salirasib 是否能增加美国食品和药物管理局批准用于胰腺癌的药物的抗肿瘤活性。
