Metal-based anticancer drugs: From a past anchored in platinum chemistry to a post-genomic future of diverse chemistry and biology

Abstract

The field of metal-based anticancer drugs was initiated by cisplatin, one of the leading agents in clinical use. Cisplatin acts by binding to DNA and forming 1,2 intrastrand cross-links. Its importance is reflected by the fact that it is estimated that 50-70 % of cancer patients are treated with a platinum drug [7]. For some time, molecular designs in the metallo-drug field remained obdurately anchored in cis-diamine platinum(II) chemistry, but now the field is evolving rapidly with a variety of alternate and very diverse designs being explored. These designs give rise to new spectra of activity and potency and can circumvent cisplatin resistance. This critical review considers the existing clinical platinum drugs, and those currently in commercial development, alongside the new designs including ruthenium anticancer and antimetastatic drugs in clinical trials, polynuclear drugs, organometallic drugs, titanium and gallium drugs, and emerging supramolecular metallo-drugs that act on DNA by noncovalent interactions. The rapid evolution of the field is being informed by post-genomic knowledge and approaches, and further dramatic step-change breakthroughs can be expected as a result; harnessing this knowledge and responding to and taking advantage of this new environment requires integration of chemistry and biology research.