Salirasib in the treatment of pancreatic cancer.

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.