Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy

1. Front Matter

   Pages i-xxvi

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2. Novel Platinum Analogues, Original Formulations and Other Heavy Metals

   1. Platinum Compounds: The Culmination of the Era of Cancer Chemotherapy

      • Franco M. Muggia

      Pages 1-7

   2. Studies on New Platinum Compounds

      • Fazlul Huq, Jun Qing Yu, Philip Beale

      Pages 11-17

   3. Assessment of the In Vivo Antiproliferative Activity of a Novel Platinum Particulate Pharmacophore

      • Elena Monti, Marzia B. Gariboldi, Raffaella Ravizza, Roberta Molteni, Elisabetta Gabano, Katia Sparnacci et al.

      Pages 19-25

   4. Nanocapsules of Platinum-Based Anticancer Drugs

      • Irene H.L. Hamelers, Anton I.P.M. de Kroon

      Pages 27-32

   5. The Design and Development of the Tumor-Targeting Nanopolymer Dach Platinum Conjugate AP5346 (Prolindac™)

      • Stephen B. Howell

      Pages 33-39

   6. In vitro Anti-proliferative Effects of ProLindac™, a Novel Dach-Platinum-Linked Polymer Compound, as a Single Agent and in Combination with Other Anti-cancer Drugs

      • Maria Serova, Aïda Ghoul, Keyvan Rezaï, François Lokiec, Esteban Cvitkovic, David Nowotnik et al.

      Pages 41-47

   7. Synthesis of Cisplatin Analogues: Cytotoxic Efficacy and Anti-tumour Activity of Bis-Amidine and Bis-Iminoether Pt(II) Complexes

      • Roberta Bertani, Silvia Mazzega Sbovata, Valentina Gandin, Rino A. Michelin, Cristina Marzano

      Pages 49-56

   8. Ruthenium Drugs for Cancer Chemotherapy: An Ongoing Challenge to Treat Solid Tumours

      • Gianni Sava, Alberta Bergamo

      Pages 57-66

   9. X-ray Crystal Structure of a Monofunctional Platinum–DNA Adduct, cis-{Pt(NH₃)₂-(Pyridine)}²⁺ Bound to Deoxyguanosine in a Dodecamer Duplex

      • Ryan C. Todd, Stephen J. Lippard

      Pages 67-72

   10. Osmium Arenes: A New Class of Potential Anti-cancer Agents

       • Sabine H. van Rijt, Anna F. A. Peacock, Peter J. Sadler

       Pages 73-79

3. Cellular Transport and Intracellular Trafficking of Platinum Compounds

   1. Resistance to Cisplatin Results from Multiple Mechanisms in Cancer Cells

      • Michael M. Gottesman, Matthew D. Hall, Xing-Jie Liang, Ding-Wu Shen

      Pages 83-88

   2. CTR1 as a Determinant of Platinum Drug Transport

      • Stephen B. Howell, Roohangiz Safaei

      Pages 89-94

   3. Regulation of the Export of Platinum-Containing Drugs by the Copper Efflux Transporters ATP7A and ATP7B

      • Roohangiz Safaei, Stephen B. Howell

      Pages 95-99

   4. Altered Localization of Transport Proteins Associated with Cisplatin Resistance

      • Ganna V. Kalayda, Ulrich Jaehde

      Pages 101-107

   5. How to Overcome Cisplatin Resistance Through Proton Pump Inhibitors

      • Angelo De Milito, Francesca Luciani, Stefano Fais

      Pages 109-114

   6. Cellular Resistance to Oxaliplatin and Drug Accumulation Defects

      • Laura Gatti, Paola Perego

      Pages 115-124

   7. Possible Incorporation of Free N7-Platinated Guanines in DNA by DNA Polymerases, Relevance for the Cisplatin Mechanism of Action

      • Michele Benedetti, Cosimo Ducani, Danilo Migoni, Daniela Antonucci, Vita M. Vecchio, Alessandro Romano et al.

      Pages 125-132

4. DNA Damage and Signal Transduction: Recognition/Repair And Cell-Response

   1. Structural and Mechanistic Studies of Anticancer Platinum Drugs: Uptake, Activation, and the Cellular Response to DNA Binding

      • Shanta Dhar, Stephen J. Lippard

      Pages 135-147

   2. Platinum Drugs and DNA Repair: Lessons from the NCI Panel and Clinical Correlates

      • Jacques Robert, Armelle Laurand, Delphine Meynard, Valérie Le Morvan

      Pages 149-155

Cisplatin, the first member of the family of platinum-containing chemotherapeutic agents, was discovered by Barnett Rosenberg in 1965 and approved by the FDA for marketing in 1978. After 30 years of use in the clinic, cisplatin remains a central element of many treatment regimens. Cisplatin is still an irreplaceable component of a regimen that produces high cure rates in even advanced nonseminomatous germ-cell cancers, and is widely used in the treatment of ovarian cancers and other gynecologic cancers, head and neck, and numerous other tumor types. The development of carboplatin has reduced some of the adverse events associated with cisplatin treatment, and the introduction of the DACH platinum compound oxaliplatin has broadened the spectrum of activity of the platinums to include gastro-intestinal cancers, especially colorectal cancer. The clinical importance of this family of drugs continues to drive investigation into how these drugs work and how to improve their efficacy and reduce their toxicity. The papers in this volume were presented in Verona, Italy, during the tenth International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy. The symposium was jointly organized by the Department of Oncology of the Mater Salutis Hospital – Azienda Sanitaria Locale 21 of the Veneto Region – and by the Department of Medicine and Public Health, Section of Pharmacology, the University of Verona. They reflect the vitality of this field and the increasing use of new molecular and cell biologic, genetic, and biochemical tools to identify approaches to further improve their use.

• Antiproliferative
• Cancer Chemotherapy
• Carcinom
• Cellular Transport
• DACH-platinum
• DNA repair
• Heavy Metal Compounds
• Pharmacophore
• Platinum
• neurotoxicity
• positron emission tomography

• Department of Oncology, Mater Salutis Hospital, Legnago, Italy

  Andrea Bonetti

• Institute of Pharmacology, University of Verona, Verona, Italy

  Roberto Leone

• Division of Medical Oncology, New York University School of Medicine and the NYU Cancer Institute, New York, USA

  Franco M. Muggia

• Department of Medicine and the Moores Cancer Center, University of California, San Diego, USA

  Stephen B. Howell

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