Nitrogen-containing bisphosphonate incadronate augments the inhibitory effect of farnesyl transferase inhibitor tipifarnib on the growth of fresh and cloned myeloma cells in vitro

RAS gene mutations occur in 30 – 40% of multiple myeloma (MM) patients. Farnesylation is the first step in the post-translational modification of RAS proteins. Tipifarnib is a potent farnesyl transferase inhibitor, and incadronate prevents post-translational prenylation of GTP-binding proteins such as RAS proteins. We examined the effect of tipifarnib in combination with incadronate on the growth of fresh and cloned myeloma cells in vitro. Tipifarnib inhibited the growth of myeloma cells, and this inhibition was intensified when tipifarnib was combined with incadronate. Tipifarnib, in combination with incadronate, may have some benefits in MM patients.