Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy

1. Front Matter

   Pages i-xi

   PDF

2. Synthetic Chemistry and Biochemistry

   1. Platinum DNA Chemistry

      • Stephen J. Lippard

      Pages 1-12

   2. New Insights About the Interaction of Cisplatinum with Intracellular Components

      • Jan Reedijk

      Pages 13-23

   3. Modelling Platinum-DNA Interactions

      • Bernhard Lippert, Gudrun Frommer, Oliver Renn, Olga Krizanovic, Iris Dieter, Michael Krumm et al.

      Pages 25-35

   4. From the Modelization of DNA Platination to the Conception of New Drugs

      • E. Segal-Bendirdjian, P. Brehin, B. Lambert, A. Laoui, J. Kozelka, J.-M. Garrot et al.

      Pages 37-49

   5. Cis-Diammineplatinum(II) Complexes Tethered to DNA-Affinic Ligands: Antitumour Activity and DNA-Binding Properties

      • Geoffrey Wickham, Laurence Wakelin, Brian Palmer, Ho Lee, Paul Johnson, Bruce Baguley et al.

      Pages 51-60

   6. Complexes of Peptides and Related Molecules with Diammineplatinum (II) as Models for Platinum-Protein Interactions

      • Trevor G. Appleton, John R. Hall, Paul D. Prenzler, Fraser B. Ross

      Pages 61-72

   7. Reactivity of DNA and cis-Diamminedichloroplatinumul(II) in the Presence of Intercalating Agents

      • Frederic Gaucheron, Marie-Agnes Lemaire, Jean Marc Malinge, Annie Schwartz, Marc Leng

      Pages 73-79

   8. Structurally Novel Platinum Antitumor Compounds

      • Nicholas Farrell

      Pages 81-91

   9. Synthesis and Reactions of a New Class of Orally Active Pt(IV) Antitumor Complexes

      • Christen M. Giandomenico, Michael J. Abrams, Barry A. Murrer, Jean F. Vollano, Christopher F. J. Barnard, Kenneth R. Harrap et al.

      Pages 93-100

   10. Pt-DNA Interactions: Oligonucleotide Models

       • Luigi Marzilli, S. Mukundan Jr., Yinghai Xu, Gerald Zon, Adelle Bergman, Paulos Yohannes et al.

       Pages 101-114

   11. New Approaches to the Design of Platinum Antitumor Agents

       • L. Steven Hollis

       Pages 115-125

   12. Developmental Approach to Prepare New Types of Antitumor Platinum Complexes with Dual Function

       • Yoshinori Kidani, Masahide Noji

       Pages 127-137

   13. Synthesis and Antitumour Activity of Some Novel Platinum(II) Organoamides and Organometallics

       • Glen B. Deacon

       Pages 139-150

3. Biochemical and Molecular Pharmacology

   1. Role of Membrane Ion Transport in Cisplatin Accumulation

      • Paul A. Andrews, Kathleen D. Albright

      Pages 151-159

   2. Enhancement of the Antiproliferative Effect of cis-Diamminedichloroplatinum (II) and Other Antitumor Agents by Inhibitors of Enzymes Involved in Growth Factor Signal-Transduction

      • Hans H. Grunicke, Johann Hofmann, Karl Maly, Hermann Oberhuber, Florian Uberall, Alexander Egle et al.

      Pages 161-172

   3. Signal Transduction Pathway Regulation of DDP Sensitivity

      • Stephen B. Howell, Seiji Isonishi, Randolph C. Christen, Paul A. Andrews, Stephen C. Mann, Doreen Hom

      Pages 173-179

   4. The Role of Platinum-DNA Lesions in the Inhibition of DNA Replication

      • N. P. Johnson, J. L. Butour, C. Cayrol, S. Cros, M. Defais, J. S. Hoffmann et al.

      Pages 181-193

   5. Activation of a Genetic Program for Cell Death

      • Alan Eastman, Michael Barry

      Pages 195-202

   6. Molecular Aspects of Repair and Mutagenesis of cis-Platinum-Induced Lesions

      • Dominique Burnouf, Corinne Gauthier, Jean-Claude Chottard, Robert P. P. Fuchs

      Pages 203-212

Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV­ induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.

• DNA
• biochemistry
• cancer treatment
• cell
• chemistry
• clinical trial
• enzymes
• ion transport
• pharmacology
• resistance
• toxicology
• tumor

• University of California, San Diego, La Jolla, USA

  Stephen B. Howell

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