Platinum-based Drugs In Cancer Therapy (cancer Drug Discovery And Development)

In Platinum-Based Drugs in Cancer Therapy, leading international experts comprehensively review all aspects of platinum anticancer drugs and their current use in treatment, as well as examining their future therapeutic prospects. Writing from a variety of disciplines, these authorities discuss the chemistry of cisplatin in aqueous solution, the molecular interaction of platinum drugs with DNA, and such exciting new areas as DNA mismatch repair, replicative bypass, apoptosis, and the transport of platinum drugs into tumor cells. The antitumor activity and toxicology of platinum-based drugs is also addressed in a thorough discussion of the clinical experience with cisplatin and carboplatin, including their promising recent combinations with taxanes and oxaliplatin. The emergent platinum drugs of the future-orally active agents, the sterically hindered ZD0473, and the polynuclear charged platinum BBR3464-are also fully considered. Timely and interdisciplinary, Platinum-Based Drugs in Cancer Therapy offers cancer therapeutics specialists an illuminating survey of every aspect of platinum drugs from mechanisms of action to toxicology, tumor resistance, and new analogs. This important book captures the essence of the fresh clinical possibilities now strongly emerging thirty years after cisplatin's discovery.

Leading international experts comprehensively review all aspects of platinum anticancer drugs and their current use in treatment, as well as examining their future therapeutic prospects. Writing from a variety of disciplines, these authorities discuss the chemistry of cisplatin in aqueous solution, the molecular interaction of platinum drugs with DNA, and such exciting new areas as DNA mismatch repair and replicative bypass, apoptosis, and the transport of platinum drugs into tumor cells. The emergent platinum drugs of the future-orally active agents, the sterically hindered ZD0473, and the polynuclear charged platinum BBR3464-are also fully considered. Timely and interdisciplinary, Platinum-Based Drugs in Cancer Therapy offers cancer therapeutics specialists an illuminating survey of every aspect of platinum drugs from mechanisms of action to toxicology, tumor resistance, and new analogs.

The book contains black-and-white illustrations.

Platinum-based cancer chemotherapy first appeared in cancer treatment literature with the landmark discovery of the anticancer activity of cisplatin. Since first publicized by Dr. Barnet Rosenberg, hundreds of new platinum-containing agents have been synthesized, with the focus on reducing side effects while retaining the antitumor activity of the parent molecule. From this molecule, carboplatin emerges as a significant new platinum-based drug with markedly less patient morbidity than cisplatin. Most recently, the focus of platinum drug development has been on the critical clinical need to broaden the number of tumor types that respond to this class of drug. Currently there are nearly 30 platinum-based drugs in clinical trials, and their structural diversity continues to expand the ongoing trials. This book merges the multidisciplinary approach of anticancer drug research with contributions from synthetic chemists, molecular biologists, pharmacologists and oncologists working to exploit the latest knowledge to further benefit cancer sufferers.

Front Matter....Pages i-xii Front Matter....Pages 1-1 The Chemistry of Cisplatin in Aqueous Solution....Pages 3-35 Chemistry and Structural Biology of 1,2-Interstrand Adducts of Cisplatin....Pages 37-61 Transplatin-modified Oligonucleotides as Potential Antitumor Drugs....Pages 63-85 Front Matter....Pages 87-87 Cisplatin Accumulation....Pages 89-113 Cisplatin Resistance in Ovarian Cancer....Pages 115-128 DNA Adduct Tolerance and Bypass....Pages 129-148 How Does Cisplatin Kill Cells?....Pages 149-167 Front Matter....Pages 169-169 Clinical Experience with Cisplatin and Carboplatin....Pages 171-194 Clinical Experience....Pages 195-230 Clinical Experience....Pages 231-249 Clinical Toxicology of Platinum-Based Cancer Chemotherapeutic Agents....Pages 251-275 Toxicology and Regulatory Aspects of Platinum Drugs....Pages 277-296 Front Matter....Pages 297-297 New Platinum Drugs....Pages 299-319 Polynuclear Charged Platinum Compounds as a New Class of Anticancer Agents....Pages 321-338 Back Matter....Pages 339-341