2.23 - Metal complexes as chemotherapeutic agents

Clinically used platinum (II) chemotherapeutics continue to dominate cancer treatment regimens 40years after the approval of cisplatin. Despite their remarkable success at treating certain types of cancers, their efficacy is still limited against others due to resistance and severe side-effects. Advances in understanding not only their mechanisms of action but also the process of carcinogenesis has made it possible to address these shortcomings through the rational design and development of fundamentally different platinum complexes. This chapter endeavors to showcase the innovative approaches researchers have undertaken in designing complexes that can act upon different cellular targets and/or disrupt biological processes that are integral to tumorigenesis. Unconventional platinum (II) complexes that deviate from the canonical structure and mechanism of cisplatin and its analogs are discussed, including monofunctional and non-covalent binders, multi-nuclear complexes and those that do not specifically bind to DNA. Multi-action platinum (IV) prodrugs that incorporate various inhibitors, exert their activity through other biological pathways, such as immunostimulatory mechanisms are also explored, in addition to photoactivatable platinum (IV) prodrugs. Some notable examples of ruthenium and gold complexes are also highlighted. With the promising outcomes exhibited by many of the metallodrugs investigated, it is envisaged that research within the field of medicinal inorganic chemistry will continue to advance, generate new knowledge and produce chemotherapeutic agents that can further improve on the current limitations of clinically used drugs.