Salirasib in the treatment of pancreatic cancer. Future Oncol 2010 Jun;6(6):885-91
Date
06/10/2010Pubmed ID
20528225DOI
10.2217/fon.10.71Scopus ID
2-s2.0-77957261391 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
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.
Author List
Bustinza-Linares E, Kurzrock R, Tsimberidou AMAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Cell Membrane
Clinical Trials, Phase I as Topic
Deoxycytidine
Disease-Free Survival
Drug Screening Assays, Antitumor
Farnesol
Farnesyltranstransferase
Galectins
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
Middle Aged
Neoplasm Proteins
Neoplasms
Pancreatic Neoplasms
Protein Binding
Protein Kinase Inhibitors
Proto-Oncogene Proteins p21(ras)
Salicylates
Signal Transduction