Cisplatin

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Thirty years after its discovery as an antitumor agent, cisplatin remains one of the most successful chemotherapy drugs. This book reflects on its history, evaluates its impact, and explores new developments in the field. Organized into six sections and 22 chapters, it covers the chemistry and biochemistry of cisplatin, the clinical status of platinum anticancer drugs, and the influence of cisplatin on inorganic and coordination chemistry. A historical chapter recounts the discovery of cisplatin, while the book addresses the ongoing question of how cisplatin induces cell death, suggesting that platinum binding to DNA may initiate a cascade leading to apoptosis, with p53 and HMG-domain proteins playing roles. The mutagenicity of platinum drugs is discussed, alongside the relevance of minor DNA adducts and the potential for trans-(NH3)2Pt(II)-modified oligonucleotides in therapeutic strategies. The extensive research on cisplatin's interactions with DNA is highlighted, showcasing advanced techniques like NMR and X-ray crystallography. The book also examines the emerging reactivity of cisplatin once bound to DNA and its significant contributions to medicinal bioinorganic chemistry. It concludes with insights into novel platinum compounds, including di- and trinuclear drugs and orally active Pt(IV) agents, as well as the integration of computational methods in studying Pt-DNA interactions.