Title:Immunomodulatory Properties of Farnesoids: The New Steroids?
Volume: 20
Issue: 10
Author(s): A. Mor, E. Aizman, J. Chapman and Y. Kloog
Affiliation:
Keywords:
Farnesylthiosalisylic acid, autoimmunity, inflammation
Abstract: Farnesylthiosalisylic acid (FTS) is a potent non-toxic anticancer drug that targets oncogenic and pathologically
activated Ras. The mechanism of action of FTS is well understood. It interferes with the binding of activated Ras proteins
to their escort chaperons and with Ras tethering to the plasma membrane. This agent has been evaluated successfully in
phase II clinical trials of pancreatic and lung cancer patients. It is generally agreed that Ras proteins play an important role
in cancer, but they also drive activation of the immune system. Therefore we hypothesized that inhibiting Ras might be
beneficial in autoimmune and inflammatory conditions. Over the past decade we have extensively studied the effects of
FTS in multiple animal models of such diseases. We were able to show potent anti-inflammatory properties of FTS in
autoimmune disease models such as systemic lupus erythematous, antiphospholipd syndrome, Guillain-Barre syndrome,
multiple sclerosis, and inflammatory bowel diseases. Its potential was also shown in type I and type II diabetes. Animal
models of contact dermatitis, allergic inflammation, and proliferative nephritis were studied as well. We have also investigated
the molecular mechanisms, signaling pathways, and inflammatory mediators underlying these conditions. In this review
we summarize our (and others) published data, and conclude that FTS has great potential as a safe anti-inflammatory
drug.
