The importance of drug resistance in cancer chemotherapy cannot be over­ stated. The 500,000 patients who die every year from cancer in the United States have, in most cases, been treated with chemotherapy. Many of these patients responded initially to chemotherapy, but death resulted from the development of drug-resistant tumors. In the first volume in the series. Drug Resistance in Chemotherapy the results of comprehensive laboratory studies aimed at understanding the mechanisms for resistance to individual agents and to the development of broad cross-resistance were described. In the past 2 years there has been substantial progress in understanding the molecular biology associated with these mechanisms of drug resistance. For the first time we are starting to understand which mechanisms are playing an im­ portant role in human tumors, and even more importantly, clinical trials have recently been initiated in an effort to reverse specific forms of drug resistance. The purpose of this volume is to describe the new advances, both at the molecular level and in the clinic regarding mechanisms of drug resistance and potential ways this resistance can be circumvented. This volume is focused upon mechanisms of resistance associated with two major classes of anticancer drugs: alkylating agents (including cisplatin) and the natural products (e. g. , adriamycin and vinblastine). The first section of the book describes new insights into the genetic mechanisms associated with drug resistance.

Inhalt

1. New Mechanisms of Gene Amplification in Drug Resistance (The Episome Model).- 2. DNA-Damage Inducible Genes.- 3. Molecular Biology of P-Glycoprotein.- 4. Resistance to Inhibitors of DNA Topoisomerases.- 5. Expression of the MDR1 Gene in Human Cancers.- 6. Immunoblot Detection of P-Glycoprotein in Human Tumors and Cell Lines.- 7. Modulators of P-Glycoprotein-Associated Multidrug Resistance.- 8. Clinical Implications of Multidrug Resistance to Chemotherapy.- 9. The Role of P-Glycoprotein in Drug-Resistant Hematologic Malignancies.- 10. DNA Repair in Drug Resistance: Studies on the Repair Process at the Level of the Gene.- 11. Mechanisms of Resistance to Cisplatin.- 12. The Role of Metallothioneins in Anticancer Drug Resistance.- 13. Modulation of Antitumor Alkylating Agents (AA).