NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetracholororuthenate, is a ruthenium(III)-based compound well known for its selective activity against solid tumour metastases. NAMI-A may bind the DNA (though at rather low an efficiency); however the effect on metastases appears to be related to modifications of the Ras-Myc signaling pathway and to the consequent significant alterations of cell angiogenesis (Brit.J.Cancer 86:993-998, 2002; Arch.Biochem.Biophys. 403:209-218, 2002; Eur.J.Biochem. in press, 2002).
NAMI-A thus suggests that metal-based compounds might be useful for signal transduction modulation, a field where the current design of future anticancer drugs bases its major expectations (1st international symposium on signal transduction modulators in cancer therapy, Amsterdam 23-25 September 2002). We might therefore expect metal-based compounds to play an important role in the new view on cancer treatment.
As yet there are no specific target-oriented approaches to prove this hypothesis, and the results obtained with NAMI-A come from studies carried on with the goal of casting light onto its metastasis-inhibiting mechanism. The lack of specifically aimed research programs, mainly due to the fact that the major interests aim elsewhere, should stress the need for challenging in a planned way the many experts in the field of bio-inorganics. The use of metal-based compounds on new targets other than nucleic acids will therefore contribute to highlighting the potential of bio-inorganic chemistry and biology as a tool to control the several actors involved in gene expression.
LINFA will contribute to this challenge by changing the models to be used in order to identify the potential of metal-based drugs as STM.

Prof. Gianni Sava