Metal Compounds in Cancer Therapy

The discovery of the antitumour activity of cisplatin in 1965 and its subsequent introduction into clinical trials in 1971 was the catalyst for a major international research effort investigating the potential of metal compounds in cancer therapy. Cisplatin now occupies an important place in the armamentarium of the oncologist due to its effectiveness in the treatment of testicular cancer. A second generation analogue, carbo platin, offers reduced toxicity together with therapeutic activity, which gives it a place in the front-line therapy of genitourinary cancers. These and other successes have encouraged the search for novel metal-based drugs for cancer therapy. Research has shown that metal compounds have potential for activity not only as cytotoxic antitumour agents, but also in areas such as adjuvant therapy, diagnosis and immunotherapy. The aim of this book is to review and describe the major achievements and developments arising from this international research effort. The contributing authors come from labora tories throughout Europe and America and represent the many disci plines characteristic of this research, such as clinical research, pharmacology, tumour biology and inorganic medicinal chemistry.

Klappentext

The discovery of the anti-tumour activity of cisplatin in 1965 and its subsequent introduction into clinical trials in 1971 was the catalyst for a major research effort into the potential of metal compounds in cancer therapy. This book draws together information on all metals involved in cancer therapy, including those used in radioisotopes. Throughout an interdisciplinary approach has been taken to reflect the nature of this research. This book will provide an invaluable reference source for anyone interested in the role of metals in oncotherapy.

Inhalt
1 Introduction.- 1.1 The Discovery of Cisplatin.- 1.2 Cancer-the Target.- 1.3 The role of Metals in Cancer Therapy.- 1.4 The Search for New Drugs.- 1.5 The Way Forward.- References.- 2 Platinum Anticancer Drugs.- 2.1 Introduction.- 2.2 Platinum Chemistry.- 2.3 Mechanism of Action.- 2.4 Platinum Pharmacology.- 2.5 Platinum Toxicology.- 2.6 The Clinical Impact of Platinum-Based Anticancer Drugs.- 2.7 The Search for New Platinum-Based Anticancer Drugs.- 2.8 Summary.- References.- 3 Gold.- 3.1 Introduction.- 3.2 Gold Chemistry.- 3.3 Gold Biochemistry and Pharmacology.- 3.4 Antitumour Activity of Auranofin and Analogues.- 3.5 [?-Bis(diphenylphosphine)ethane]Digold Species.- 3.6 Bis[1,2-bis(diphenylphosphino)ethane]Gold(I)and Related Complexes, [Au(P-P)2]+.- 3.7 Gold Complexes of Known Antitumour Agents.- 3.8 Other Active Compounds.- 3.9 Cisplatin Analogues.- 3.10 Conclusions.- Acknowledgement.- References.- 4 Ruthenium Compounds in Cancer Therapy.- 4.1 Introduction.- 4.2 Chemical Properties Relevant to Tumour Treatment.- 4.3 Effects on Cancer Growth.- 4.4 Conclusions.- Acknowledgement.- References.- 5 Rhodium, Iridium and Palladium Compounds as Experimental Anticancer Drugs.- 5.1 Introduction.- 5.2 Rhodium.- 5.3 Iridium.- 5.4 Palladium.- 5.5 Comments.- References.- 6 Organometallic Titanium, Vanadium, Niobium, Molybdenum and Rhenium Complexes - Early Transition Metal Antitumour Drugs.- 6.1 Introduction.- 6.2 Antitumour Activity of Titanocene and Vanadocene Dichlorides, Two Neutral Organometallic Complexes of Early Transition Metals.- 6.3 Antitumour Activity of Ionic Titanocene Complexes, Another Type of Organometallic Early Transition Metal Compound.- 6.4 Toxicological and Pharmacokinetic Properties of Neutral Titanocene and Vanadocene Dichloride Complexes.- 6.5 Phase IClinical Trial with Titanocene Dichloride.- 6.6 Antitumour Activity of Ionic Niobocene, Molybdenocene and Rhenocene Complexes, Newly Developed Organometallic Early Transition Metal Complexes.- 6.7 Antitumour Activity of Inorganic Bis(?-diketonato)-Titanium Complexes in Preclinical and Phase I Clinical Trials.- 6.8 Summary and Outlook.- Acknowledgements.- References.- 7 Antitumour Activity of Tin Compounds.- 7.1 Introduction.- 7.2 Early Antitumour Studies Involving Metal Derivatives.- 7.3 Tin Analogues of Cisplatin.- 7.4 Other in Vivo Studies Involving Tin Compounds.- 7.5 In Vitro Studies using Tin Derivatives.- 7.6 Mode of Action.- 7.7 The use of Tin Derivatives in the Photodynamic Therapy of Cancer.- 7.8 Concluding remarks.- Acknowledgements.- References.- 8 Gallium Compounds in Cancer Therapy.- 8.1 Introduction.- 8.2 In Vitro Studies.- 8.3 In Vivo Studies.- 8.4 Clinical Studies.- References.- 9 Bleomycin and Metal Interactions.- 9.1 Introduction.- 9.2 The Activation of Oxygen to Reactive Intermediates by Transition Metal Ions.- 9.3 Binding of Metal Ions to Bleomycin.- 9.4 Binding of Bleomycin to DNA.- 9.5 The Antitumour Activity of Bleomycin.- 9.6 Bleomycin used as a Biological Tool to Detect and Measure Low Molecular Mass Iron in Body Fluids.- Acknowledgements.- References.- 10 The in vivo use of Metallic Radioisotopes in Cancer Detection and imaging.- 10.1 Introduction.- 10.2 Tumour Imaging Applications of Simple Chelates.- 10.3 Tumour Imaging and Therapeutic Applications of Bifunctional Chelates.- 10.4 Radioisotopes.- 10.5 Novel Pretargeting Approaches.- 10.6 Conclusions.- References.