Enhancing FTS (Salirasib) efficiency via combinatorial treatment.
The Ras oncogene transmits signals, which regulate various cellular processes including cell motility, differentiation, growth and death. Since Ras signalling is abnormally activated in more than 30% of human cancers, Ras and its downstream signalling pathways are considered good targets for therapeutic interference. Ras is post-translationally modified by the addition of a farnesyl group, which permits its attachment to the plasma membrane. Exploiting this knowledge, a synthetic Ras inhibitor, S-trans, trans-farnesylthiosalicylic acid (FTS; Salirasib), was developed. FTS resembles the farnesylcysteine group of Ras, and acts as an effective Ras antagonist. In the present review, the effect of FTS in combination with various other drugs, as tested in vitro and in vivo, and its therapeutic potential are discussed. As reviewed, FTS cooperates with diverse therapeutic agents, which significantly improves treatment outcome. Therefore, combinations of FTS with other agents have a potential to serve as anti-cancer or anti-inflammatory therapies.
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel.
Eya
E
Wolfson
Eran
E
Schmukler
Sari Trangle
ST
Schokoroy
Yoel
Y
Kloog
Ronit
R
Pinkas-Kramarski
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D005204:Farnesol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol
Apoptosis; Cancer; Cell death; Diseases; G-proteins