Changing the chemical structure of platinum compounds may substantially modulate their DNA-binding mode, subsequent processing of DNA damage and consequently the mechanism of biological efficacy of these compounds. These structural modifications may also affect the spectrum of biological activity of the platinum agents, the development of drug resistance, and also their toxicity profile. Hence, a further understanding of how new platinum compounds modify DNA and how these modifications are further processed in cells may lead to further insight of 'downstream' effects, initiated through differential protein recognition and repair, that may produce unique biological effects. On the other hand, there is still a gap between these molecular events involving DNA interactions and an understanding as to why platinum anticancer drugs are more poisonous to cancer cells than to normal cells. The studies so far performed in this area have implicated multiple systems including several classes of DNA repair, replication, transcription, cell cycle and cell death responses involved in the processes associated with cellular sensitivity to the platinum drugs. It is also likely that many other determinants remain to be identified. Complete knowledge of how modifications of DNA by anti-tumor platinum compounds and other metal-based drugs affect the components of these pathways should provide a basis for understanding the mechanism of action of platinum drugs and, thereby, a rational basis for the design of new metal-based drugs and to identify optimal treatment strategies.
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